In vivo MRI reveals the dynamics of pathological changes in the brains of cathepsin D-deficient mice and correlates changes in manganese-enhanced MRI with microglial activation

Cathepsin D (CTSD; EC 3.4.23.5) is essential for normal development and/or maintenance of neurons in the central nervous system: its deficiency causes a devastating neurological disorder with severely shortened life span in man, sheep and mouse. Neuropathologically, the CTSD deficiencies are characterized by selective neuronal degeneration, gliosis and accumulation of autofluorescent proteinaceous storage material in neurons. Our aim was to study the dynamics behind the pathological alterations occurring in the brains of CTSD-deficient (CTSD-/-) mice by using in vivo magnetic resonance imaging (MRI) and histology. In order to do this, we measured T(2) signal intensity (SI), apparent diffusion coefficient, area and volume of multiple brain structures from MR images acquired using T(2)-, T(1)- and diffusion-weighted sequences at three time points during disease progression. MRI revealed no differences in the brains between CTSD-/- and control mice at postnatal day 15+/-1 (P15+/-1), representing an initial stage of the disease. In the intermediate stage of the disease, P19(+/-1), SI alterations in the thalami of the affected mice became evident in both T(1)- and T(2)-weighted images. The terminal stage of the disease, P25, was characterized by marked alterations in the T(2) SI, apparent diffusion coefficient and volume of multiple brain structures in CTSD-/- mice. In addition, manganese enhanced high-resolution T(1)-weighted 3D sequences (MEMRI) and histological stainings revealed that the hyperintense signal areas in MEMRI matched perfectly with areas of microglial activation in the brains of CTSD-/- mice at the terminal disease stage. In conclusion, the SI alterations in the thalami of CTSD-/- mice preceded other changes, and the degenerative process was greatly enhanced at the age P19(+/-1), leading to severely reduced brain volume in just 6 days.     

Enhancements in 3D dosimetry measurement using polymer gel and MRI

The effects of varying the concentrations of cross-linker N, $N^{\prime }$-methyelene-bis-acrylamide (BIS) from 2% to 4%, and 2-hydroxyethylacrylate (HEA) monomer from 2% to 4% at 5% gelatin on the dose response of BIS–HEA–gelatin (BHEAG) aqueous polymer gel dosimeters have been studied using magnetic resonance imaging (MRI) for relaxation rate ($R_2)$ of water proton. The dosimeters were irradiated with ⁶⁰Co teletherapy $\gamma$-ray source at a constant dose rate, receiving doses up to 30 Gy. The radiation polymerization occurs and increases with increasing initial dose. $R_2$ is found to decrease mono-exponentially with depth inside the polymer gel and depend strongly upon the initial concentrations of co-monomers (HEA and BIS). Dose–depth map for BHEAG gel was determined for different concentrations of co-monomer (HEA and BIS). The percentage dose depth was also evaluated which leads to a good agreement with the ionization chamber measurements.     

In vivo isotropic 3D diffusion tensor mapping of the rat brain using diffusion-weighted 3D MP-RAGE MRI

The purpose of this study was to examine the potential of diffusion-weighted (DW) three-dimensional (3D) MP-RAGE MRI for diffusion-tensor mapping of the rat brain in vivo. A DW-3D-MP-RAGE (3D-DWI) sequence was implemented at 2.0 T using six gradient orientations and a b value of 1000 s/mm2. In this sequence, the preparation sequence with a "90 degrees RF-motion proving gradient (MPG): MPG-180 degrees RF-MPG-90 degrees RF" pulse train (DW driven equilibrium Fourier transform) was used to sensitize the magnetization to diffusion. A centric k-space acquisition order was necessary to minimize saturation effects (T1 contamination) from tissues with short relaxation time. The image matrix was 128x128x128 (interpolated from 64x64x64 acquisitions), which resulted in small isotropic DW image data (voxel size: 0.273x0.273x0.273 mm3). Moreover, 3D-DWI-derived maps of the fractional anisotropy (FA), relative anisotropy (RA) and main-diffusion direction were completely free of susceptibility-induced signal losses and geometric distortions. Two well-known commissural fibers, the corpus callosum and anterior commissure, were indicated and shown to be in agreement with the locations of these known stereotaxic atlases. The experiment took 45 min, and shorter times should be possible in clinical application. The 3D-DWI sequence allows for in vivo 3D diffusion-tensor mapping of the rat brain without motion artifacts and susceptibility to distortion.     

Automatic 3D tracking of cardiac material markers using slice-following and harmonic-phase MRI

A method to track a grid of cardiac material points in three dimensions using slice-following (SF) tagged magnetic resonance imaging (MRI) and harmonic-phase MRI is presented. A three-dimensional grid of material points on the lines of intersections of short-axis (SA) and long-axis (LA) planes is automatically tracked by combining two-dimensional pathlines that are computed on both SA and LA image planes. This process yields the true three-dimensional motion of points originating on the image plane intersections. Experimental data from normal volunteers, each obtained in four short breath-holds using the SF harmonic phase MRI pulse sequence, is presented. A validation of two-dimensional in-plane tracks using this pulse sequence on a moving phantom is also presented.     

Geometric distortion in clinical MRI systems Part II: correction using a 3D phantom

In this paper, we present the correction of the geometric distortion measured in the clinical magnetic resonance imaging (MRI) systems reported in the preceding paper (Part I) using a 3D method based on the phantom-mapped geometric distortion data. This method allows the correction to be made on phantom images acquired without or with the vendor correction applied. With the vendor's 2D correction applied, the method corrects for both the "residual" geometric distortion still present in the plane in which the correction method was applied (the axial plane) and the uncorrected geometric distortion along the axis normal to the plane. The evaluation of the effectiveness of the correction using this new method was carried out through analyzing the residual geometric distortion in the corrected phantom images. The results show that the new method can restore the distorted images in 3D nearly to perfection. For all the MRI systems investigated, the mean absolute deviations in the positions of the control points (along x-, y- and z-axes) measured on the corrected phantom images were all less than 0.2 mm. The maximum absolute deviations were all below approximately 0.8 mm. As expected, the correction of the phantom images acquired with the vendor's correction applied in the axial plane performed equally well. Both the geometric distortion still present in the axial plane after applying the vendor's correction and the uncorrected distortion along the z-axis have all been "restored."     

Geometric distortion in clinical MRI systems Part I: evaluation using a 3D phantom

Recently, a 3D phantom that can provide a comprehensive and accurate measurement of the geometric distortion in MRI has been developed. Using this phantom, a full assessment of the geometric distortion in a number of clinical MRI systems (GE and Siemens) has been carried out and detailed results are presented in this paper. As expected, the main source of geometric distortion in modern superconducting MRI systems arises from the gradient field nonlinearity. Significantly large distortions with maximum absolute geometric errors ranged between 10 and 25 mm within a volume of 240 x 240 x 240 mm(3) were observed when imaging with the new generation of gradient systems that employs shorter coils. By comparison, the geometric distortion was much less in the older-generation gradient systems. With the vendor's correction method, the geometric distortion measured was significantly reduced but only within the plane in which these 2D correction methods were applied. Distortion along the axis normal to the plane was, as expected, virtually unchanged. Two-dimensional correction methods are a convenient approach and in principle they are the only methods that can be applied to correct geometric distortion in a single slice or in multiple noncontiguous slices. However, these methods only provide an incomplete solution to the problem and their value can be significantly reduced if the distortion along the normal of the correction plane is not small.     

Response of bilateral breasts to the endogenous hormonal fluctuation in a menstrual cycle evaluated using 3D MRI

The normal breast tissue responds to the fluctuation of endogenous hormones during a menstrual cycle (MC) and shows changes in breast density. The changes between left and right breasts of the same women were compared to evaluate the symmetrical response. Twenty-four healthy women were recruited in this study. Four weekly magnetic resonance imaging (MRI) studies were performed during one MC. A computer algorithm was used to segment the breast and the fibroglandular tissue to measure the fibroglandular tissue volume (FV) and three morphological parameters: circularity, convexity and irregularity. The coefficient of variation (CV) for each parameter measured among four MRI studies was calculated; also, the maximal percent change between two MRI studies that show the highest and the lowest FV was calculated. These parameters measured from left and right breasts were compared using Pearson correlation.     

Dynamic sequential 3D gadolinium-enhanced MRI of the whole breast

Dynamic contrast-enhanced 2D MR imaging of the breast has shown high sensitivity and specificity for the detection and characterization of breast lesions. We investigated the ability of a dynamic fast 3D MR imaging technique that repeatedly scans the whole breast in 44-s intervals without an interscan delay time to obtain similar sensitivity and specificity as 2D imaging. Fifty-six patients scheduled for breast biopsy were entered into the study, and 83 lesions detected by 3D dynamic scanning were biopsied. Dynamic 3D contrast-enhanced breast imaging with subtraction detected and correctly classified all 23 cancers, and 44 of the 60 benign lesions yielding a sensitivity of 100%, a specificity of 73%, and a 100% predictive negative value. The enhancement profiles of metastatic lymph nodes were similar to those of primary cancer. This technique allowed detection of multifocal and multicentric lesions and did not require a priori knowledge of lesion location. These results indicate that dynamic contrast-enhanced 3D MRI of the whole breast is a useful and economically feasible method for staging breast cancer, providing a comprehensive noninvasive method for total evaluation of the breast and axilla in patients considering breast conservation surgery or lumpectomy.     

3D micron-scale MRI of single biological cells

We report MRI microscopy images of single biological cells with micron-scale resolution in all three dimensions. Sub-cellular organelles are observed, including a spiral-shaped array of chloroplasts on the inner surface of the cell wall of a Spirogyra alga.     

Improvement of 3D acquisition and visualization in MRI.

Three-dimensional (3D) visualization techniques are becoming an ever more important aid in the interpretation of tomographic data. Up to now, however, they have not received widespread use in MRI, because both acquisition and visualization techniques have been inadequate. In this paper we describe new 3D acquisition techniques which can acquire up to 128 slices with a resolution of 256 x 256 pixels in from 8 to 20 min. These techniques produce 3D data sets with excellent contrast and few motion artifacts, which are very well suited for 3D visualization techniques. For the visualization we investigate several rendering techniques, describe some improvements and compare their results. We found that there is no single method which renders all objects equally well. We show which shading method is best suited for different objects and why the other methods fail. Our studies suggest that in a 3D view with several objects each object should be rendered with a separate shading method. In so doing, 3D views can be generated which look like the real human anatomy.     

3D MRI of non-Gaussian (3)He gas diffusion in the rat lung

In (3)He magnetic resonance images of pulmonary air spaces, the confining architecture of the parenchymal tissue results in a non-Gaussian distribution of signal phase that non-exponentially attenuates image intensity as diffusion weighting is increased. Here, two approaches previously used for the analysis of non-Gaussian effects in the lung are compared and related using diffusion-weighted (3)He MR images of mechanically ventilated rats. One approach is model-based and was presented by Yablonskiy et al., while the other approach utilizes the second order decay contribution that is predicted from the cumulant expansion theorem. Total lung coverage is achieved using a hybrid 3D pulse sequence that combines conventional phase encoding with sparse radial sampling for efficient gas usage. This enables the acquisition of nine 3D images using a total of only approximately 1 L of hyperpolarized (3)He gas. Diffusion weighting ranges from 0 s/cm(2) to 40 s/cm(2). Results show that the non-Gaussian effects of (3)He gas diffusion in healthy rat lungs are directly attributed to the anisotropic geometry of lung microstructure as predicted by the Yablonskiy model, and that quantitative analysis over the entire lung can be reliably repeated in time-course studies of the same animal.     

Volumetric q-space imaging by 3D diffusion-weighted MRI

High b-value diffusion magnetic resonance imaging (MRI) enables us to detect far smaller architectures, by using q-space analysis, than the resolution in conventional MRI. Average displacement, one of the q-space parameters, quantitatively reflects architecture size and is very useful in observing small changes in microstructures in vivo (e.g., neurodegeneration, tumor heterogeneity, and others). Diffusion-weighted imaging (DWI) is performed by a two-dimensional (2D) multislice method; however, due to finite slice thickness and slice gap, there is a partial-volume effect that makes it difficult to detect the net q-space signal. On the other hand, three-dimensional (3D) MRI, having the advantages of very thin slice thickness and no slice gap (contiguous slices), allows volumetric evaluation acquired in a small isotropic voxel, as compared to 2D multislice imaging. Little is known about the isotropic high-resolution 3D DWI application to q-space analysis. In this study, we have developed and implemented a high b-value 3D DWI sequence, applied q-space analysis to study the reliability of high b-value 3D DWI and obtained a microscopic analytical map with isotropic high resolution and less contamination.     

A fast screening protocol for carotid plaques imaging using 3D multi-contrast MRI without contrast agent

PurposeTo implement a fast (~ 15 min) MRI protocol for carotid plaque screening using 3D multi-contrast MRI sequences without contrast agent on a 3 Tesla MRI scanner.Materials and methods7 healthy volunteers and 25 patients with clinically confirmed transient ischemic attack or suspected cerebrovascular ischemia were included in this study. The proposed protocol, including 3D T1-weighted and T2-weighted SPACE (variable-flip-angle 3D turbo spin echo), and T1-weighted magnetization prepared rapid acquisition gradient echo (MPRAGE) was performed first and was followed by 2D T1-weighted and T2-weighted turbo spin echo, and post-contrast T1-weighted SPACE sequences. Image quality, number of plaques, and vessel wall thicknesses measured at the intersection of the plaques were evaluated and compared between sequences.ResultsAverage examination time of the proposed protocol was 14.6 min. The average image quality scores of 3D T1-weighted, T2-weighted SPACE, and T1-weighted magnetization prepared rapid acquisition gradient echo were 3.69, 3.75, and 3.48, respectively. There was no significant difference in detecting the number of plaques and vulnerable plaques using pre-contrast 3D images with or without post-contrast T1-weighted SPACE. The 3D SPACE and 2D turbo spin echo sequences had excellent agreement (R = 0.96 for T1-weighted and 0.98 for T2-weighted, p < 0.001) regarding vessel wall thickness measurements.ConclusionThe proposed protocol demonstrated the feasibility of attaining carotid plaque screening within a 15-minute scan, which provided sufficient anatomical coverage and critical diagnostic information. This protocol offers the potential for rapid and reliable screening for carotid plaques without contrast agent.     

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.     

Clinical value of routine use of thin-section 3D MRI using 3D FSE sequences with a variable flip angle technique for internal derangements of the knee joint at 3T

PurposeTo determine the clinical value of routine use of thin-section 3D MRI using 3D FSE sequences with a variable flip angle technique for internal derangements of the knee joint at 3 T.Method and MaterialsThirty-four knees in 34 patients suspected of having internal derangements of the knee joint were included. Following standard 2D MRI protocol including sagittal PDWI, T1WI and T2*WI, coronal fat-suppressed PDWI, and axial fat-suppressed PDWI with 3-4 mm thicknesses, fat-suppressed and water-excitation PDWI using 3D FSE sequences with a variable flip angle technique with 0.6 mm thickness were obtained in coronal plane and the three major planes with 1 mm thickness (3D MRI) was reformatted. The standard 2D MRI protocol and reformatted 3D MRI protocol (three sagittal 2D sequence images plus 3D MRI) were independently analyzed by two radiologists concerning presence or absence of lesions in the menisci, cartilage, and ligament. Interobserver agreements in both the MRI protocols were assessed by weighted-kappa coefficients. Regarding diagnostic accuracy, areas under the receiver operating characteristic curves (Az values) of both the MRI protocols were compared.ResultsThirty-eight meniscal lesions, 39 cartilage lesions, and 20 ligamentous lesions were surgically detected. Excellent interobserver agreements (kappa = 0.91–0.98) were seen in both the MRI protocols, with a slightly better tendency in the reformatted 3D MRI protocol. Average Az values in detection of the meniscal, cartilage, and ligamentous lesions were significantly higher in the reformatted 3D MRI protocol than in the standard 2D MRI protocol (p < 0.01 or p < 0.001).ConclusionRoutine use of reformatted thin-section 3D MRI using 3D FSE sequences with a variable flip angle technique may improve diagnostic accuracy and confidence in detection of internal derangements of the knee joint.     

A practical and flexible implementation of 3D MRI in the Earth's magnetic field

The Earth's magnetic field, though weak, is appealing for NMR applications because it is highly homogeneous, globally available and free. However, the practicality of Earth's field NMR (EFNMR) has long been limited by the need to perform experiments in outdoor locations where the local field homogeneity is not disrupted by ferrous or magnetic objects and where ultra-low frequency (ULF) noise sources are at a minimum. Herein we present a flexible and practical implementation of MRI in the Earth's magnetic field that demonstrates that EFNMR is not as difficult as it was previously thought to be. In this implementation, pre-polarization and ULF noise shielding, achieved using a crude electromagnet, are used to significantly improve signal-to-noise ratio (SNR) even in relatively noisy environments. A three axis gradient coil set, in addition to providing imaging gradients, is used to provide first-order shims such that sub-hertz linewidths can routinely be achieved, even in locations of significant local field inhomogeneity such as indoor scientific laboratories. Temporal fluctuations in the magnitude of the Earth's magnetic field are measured and a regime found within which these variations in Larmor frequency produce no observable artefacts in reconstructed images.     

Compression and reconstruction of MRI images using 2D DCT.

In magnetic resonance imaging (MRI), the original data are sampled in the spatial frequency domain. The sampled data thus constitute a set of discrete Fourier transform (DFT) coefficients. The image is usually reconstructed by taking inverse DFT. The image data may then be compressed using the discrete cosine transform (DCT). We present here a method of treating the data that combines two procedures, image reconstruction and data compression. This method may be particularly useful in medical picture archiving and communication systems (PACS) where both image reconstruction and compression are important issues.     

Mapping of left ventricle wall thickness in mice using 11.7-T magnetic resonance imaging

BackgroundThe left ventricle (LV) wall thickness is an important and routinely measured cardiologic parameter. Here we introduce three-dimensional (3D) mapping of LV wall thickness and function using a self-gated magnetic resonance (MR) sequence for ultra-high-field 11.7-T MR cine imaging of mouse hearts.Methods and resultsSix male C57BL/6-j mice were subjected to 11.7-T MR imaging (MRI). Three standard views—short axis, long axis four-chamber, and long axis two-chamber—and eight consecutive short axis scans from the apex to base were performed for each mouse. The resulting 11 self-gated cine images were used for fast low-angle shot analysis with a navigator echo over an observation period of approximately 35 min. The right ventricle (RV) and LV were identified in the short axis and four-chamber views. On 3D color-coded maps, the interventricular septum wall (diastole: 0.94 ± 0.05 mm, systole: 1.20 ± 0.09 mm) and LV free wall (diastole: 1.07 ± 0.15 mm, systole: 1.79 ± 0.11 mm) thicknesses were measured.ConclusionThis 3D wall thickness mapping technique can be used to observe regional wall thickness at the end-diastole and end-systole. Self-gated cine imaging based on ultra-high-field MRI can be used to accurately and easily measure cardiac function and wall thickness in normal mouse hearts. As in the preclinical study, this versatile and simple method will be clinically useful for the high-field-MRI evaluation of cardiac function and wall thickness.     

Assessment of cerebral blood perfusion reserve with acetazolamide using 3D spiral ASL MRI: Preliminary experience in pediatric patients

PurposeTo demonstrate the clinical feasibility of a new non-Cartesian cylindrically-distributed spiral 3D pseudo-continuous arterial spin labeling (pCASL) magnetic resonance imaging (MRI) pulse sequence in pediatric patients in quantifying cerebral blood flow (CBF) response to an acetazolamide (ACZ) vasodilator challenge.Materials and methodsMRI exams were performed on two 3 Tesla Philips Ingenia systems using 32 channel head coil arrays. After local institutional review board approval, the 3D spiral-based pCASL technique was added to a standard brain MRI exam and evaluated in 13 pediatric patients (average age: 11.7 ± 6.4 years, range: 1.4–22.2 years). All patients were administered ACZ for clinically indicated reasons. Quantitative whole-brain CBF measurements were computed pre- and post-ACZ to assess cerebrovascular reserve.Results3D spiral pCASL data were successfully reconstructed in all 13 cases. In 11 patients, CBF increased 2.8% to 93.2% after administration of ACZ. In the two remaining patients, CBF decreased by 2.4 to 6.0% after ACZ. The group average change in CBF due to ACZ was approximately 25.0% and individual changes were statistically significant (p < 0.01) in all patients using a paired t-test analysis. CBF perfusion data were diagnostically useful in supporting conventional MR angiography and clinical findings.Conclusion3D cylindrically-distributed spiral pCASL MRI provides a robust approach to assess cerebral blood flow and reserve in pediatric patients.