In vivo visualization of Alzheimer's amyloid plaques by magnetic resonance imaging in transgenic mice without a contrast agent.

One of the cardinal pathologic features of Alzheimer's disease (AD) is the formation of senile, or amyloid, plaques. Transgenic mice have been developed that express one or more of the genes responsible for familial AD in humans. Doubly transgenic mice develop "human-like" plaques, providing a mechanism to study amyloid plaque biology in a controlled manner. Imaging of labeled plaques has been accomplished with other modalities, but only MRI has sufficient spatial and contrast resolution to visualize individual plaques noninvasively. Methods to optimize visualization of plaques in vivo in transgenic mice at 9.4 T using a spin echo sequence based on adiabatic pulses are described. Preliminary results indicate that a spin echo acquisition more accurately reflects plaque size, while a T2* weighted gradient echo sequence reflects plaque iron content, not plaque size. In vivo MRI-ex vivo MRI-in vitro histologic correlations are provided. Histologically verified plaques as small as 50 microm in diameter were visualized in living animals. To our knowledge this work represents the first demonstration of noninvasive in vivo visualization of individual AD plaques without the use of a contrast agent.     

Detection of amyloid plaques in mouse models of Alzheimer's disease by magnetic resonance imaging.

We performed three-dimensional, high-resolution magnetic resonance imaging (MRI) of fixed mouse brains to determine whether MRI can detect amyloid plaques in transgenic mouse models of Alzheimer's disease. Plaque-like structures in the cortex and hippocampus could be clearly identified in T2-weighted images with an image resolution of 46 microm x 72 microm x 72 microm. The locations of plaques were confirmed in coregistration studies comparing MR images with Congo red-stained histological results. This technique is quantitative, less labor-intensive compared to histology, and is free from artifacts related to sectioning process (deformation and missing tissues). It enabled us to study the distribution of plaques in the entire brain in 3D. The results of this study suggest that this method may be useful for assessing treatment efficacy in mouse models of Alzheimer's disease (AD).     

Positive contrast imaging of iron oxide nanoparticles with susceptibility‐weighted imaging

Superparamagnetic iron oxide particles can be utilized to label cells for immune cell and stem cell therapy. The labeled cells cause significant field distortions induced in their vicinity, which can be detected with magnetic resonance imaging (MRI). In conventional imaging, the signal voids arising from the field distortions lead to negative contrast, which is not desirable, as detection of the cells can be masked by native low signal tissue. In this work, a new method for visualizing magnetically labeled cells with positive contrast is proposed and described. The technique presented is based on the susceptibility‐weighted imaging (SWI) post‐processing algorithm. Phase images from gradient‐echo sequences are evaluated pixel by pixel, and a mask is created with values ranging from 0 to 1, depending on the phase value of the pixel. The magnitude image is then multiplied by the mask. With an appropriate mask function, positive contrast in the vicinity of the labeled cells is created. The feasibility of this technique is proved using an agar phantom containing superparamagnetic iron oxide particles–labeled cells and an ex vivo bovine liver. The results show high potential for detecting even small labeled cell concentrations in structurally inhomogeneous tissue types. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Human imaging at 9.4 T using T2*‐, phase‐, and susceptibility‐weighted contrast

The effect of susceptibility differences on an MR image is known to increase with field strength. Magnetic field inhomogeneities within the voxels influence the apparent transverse relaxation time T₂*, while effects due to different precession frequencies between voxels caused by local field variations are evident in the image phase, and susceptibility‐weighted imaging highlights the veins and deep brain structures. Here, these three contrast mechanisms are examined at a field strength of 9.4 T. The T₂* maps generated allow the identification of white matter structures not visible in conventional images. Phase images with in‐plane resolutions down to 130 μm were obtained, showing high gray/white matter contrast and allowing the identification of internal cortical structures. The susceptibility‐weighted images yield excellent visibility of small venous structures and attain an in‐plane resolution of 175 μm. Magn Reson Med, 2011. © 2010 Wiley‐Liss, Inc.     

Visualization of beta-amyloid plaques in a transgenic mouse model of Alzheimer's disease using MR microscopy without contrast reagents.

The visualization of beta-amyloid plaque deposition in brain, a key feature of Alzheimer's disease (AD), is important for the evaluation of disease progression and the efficacy of therapeutic interventions. In this study, beta-amyloid plaques in the PS/APP transgenic mouse brain, a model of human AD pathology, were detected using MR microscopy without contrast reagents. beta-Amyloid plaques were clearly visible in the cortex, thalamus, and hippocampus of fixed brains of PS/APP mice. The distribution of plaques identified by MRI was in excellent agreement with those found in the immunohistological analysis of the same brain sections. It was also demonstrated that image contrast for beta-amyloid plaques was present in freshly excised nonfixed brains. Furthermore, the detection of beta-amyloid plaques was achieved with a scan time as short as 2 hr, approaching the scan time considered reasonable for in vivo imaging.     

Diminished visibility of cerebral venous vasculature in multiple sclerosis by susceptibility‐weighted imaging at 3.0 Tesla

Multiple sclerosis (MS) is a disease of the central nervous system characterized by widespread demyelination, axonal loss and gliosis, and neurodegeneration; susceptibility‐weighted imaging (SWI), through the use of phase information to enhance local susceptibility or T2* contrast, is a relatively new and simple MRI application that can directly image cerebral veins by exploiting venous blood oxygenation. Here, we use high‐field SWI at 3.0 Tesla to image 15 patients with clinically definite relapsing‐remitting MS and to assess cerebral venous oxygen level changes. We demonstrate significantly reduced visibility of periventricular white matter venous vasculature in patients as compared to control subjects, supporting the concept of a widespread hypometabolic MS disease process. SWI may afford a noninvasive and relatively simple method to assess venous oxygen saturation so as to closely monitor disease severity, progression, and response to therapy. J. Magn. Reson. Imaging 2009;29:1190–1194. © 2009 Wiley‐Liss, Inc.     

Longitudinal assessment of Alzheimer's beta-amyloid plaque development in transgenic mice monitored by in vivo magnetic resonance microimaging

PURPOSE: To assess the development of beta-amyloid (Abeta) plaques in the brain with age in the transgenic mouse model of Alzheimer's disease (AD) pathology by in vivo magnetic resonance microimaging (microMRI). MATERIALS AND METHODS: Live transgenic mice (Tg2576) and nontransgenic littermates (control) were studied at regular intervals between the ages of 12 and 18 months. Plaques were visualized using a T(2)-weighted rapid acquisition with relaxation enhancement (RARE) sequence. Changes in T(2) relaxation times were followed using a multislice multiecho (MSME) sequence. Plaque load and numerical density in MR images were calculated using SCIL image software. RESULTS: Abeta plaques were clearly detected with the T(2)-weighted RARE sequence in the hippocampal and cortical regions of the brain of Tg2576 mice but not in control mice. Following the plaque development in the same animals with age showed that plaque area, number, and size increased markedly, while T(2) relaxation time showed a decreasing trend with age. CONCLUSION: These results demonstrate that microMRI is a viable method for following the development of Abeta plaques in vivo, and suggest that this method may be feasible for assessing the effect of therapeutic interventions over time in the same animals.     

Detection of normal spinal veins by using susceptibility‐weighted imaging

Purpose:

To evaluate the visualization of the spinal veins using susceptibility‐weighted imaging (SWI).

Materials and Methods:

A 1.5‐T magnet equipped with a spine matrix coil was used. Axial SWI scans of 20 healthy volunteers were obtained with a three‐dimensional fast low‐angle shot (3D‐FLASH) sequence. Maximum intensity projection (MIP) of the phase images were reconstructed and five MIP images (at the levels of T11, T11/12, T12, T12/L1, and L1) were selected for the evaluation. The anterior median vein (AMV), posterior median vein (PMV), anterior radiculomedullary vein (ARV), posterior radiculomedullary vein (PRV), and sulcal vein (SV) were evaluated using a 4‐grade scale (0, none; 1, weak; 2, moderate; and 3, prominent).

Results:

The AMV was detected in all the subjects (100%). The detection rates of the other veins were lower: PMV, 65%; right ARV, 45%; left ARV, 15%; right PRV, 10%; left PRV, 30%; and SV, 0%. The average scores for AMV, PMV, right ARV, left ARV, right PRV, left PRV, and SV were 0.98, 0.24, 0.20, 0.08, 0.08, 0.14, and 0, respectively.

Conclusion:

SWI of the spine is feasible. The extrinsic spinal veins can be visualized by SWI without using contrast materials. J. Magn. Reson. Imaging 2010;31:32–38. © 2009 Wiley‐Liss, Inc.     

MRI assessment of neuropathology in a transgenic mouse model of Alzheimer's disease.

The cerebral deposition of amyloid beta-peptide, a central event in Alzheimer's disease (AD) pathogenesis, begins several years before the onset of clinical symptoms. Noninvasive detection of AD pathology at this initial stage would facilitate intervention and enhance treatment success. In this study, high-field MRI was used to detect changes in regional brain MR relaxation times in three types of mice: 1). transgenic mice (PS/APP) carrying both mutant genes for amyloid precursor protein (APP) and presenilin (PS), which have high levels and clear accumulation of beta-amyloid in several brain regions, starting from 10 weeks of age; 2). transgenic mice (PS) carrying only a mutant gene for presenilin (PS), which show subtly elevated levels of Abeta-peptide without beta-amyloid deposition; and 3). nontransgenic (NTg) littermates as controls. The transverse relaxation time T(2), an intrinsic MR parameter thought to reflect impaired cell physiology, was significantly reduced in the hippocampus, cingulate, and retrosplenial cortex, but not the corpus callosum, of PS-APP mice compared to NTg. No differences in T(1) values or proton density were detected between any groups of mice. These results indicate that T(2) may be a sensitive marker of abnormalities in this transgenic mouse model of AD.     

Detecting lesions in multiple sclerosis at 4.7 tesla using phase susceptibility‐weighting and T2‐weighting

Purpose

To demonstrate 4.7 Tesla (T) imaging methods for visualizing lesions in multiple sclerosis in the human brain using phase susceptibility‐weighting and T2 weighting.

Materials and Methods

Seven patients with relapsing‐remitting multiple sclerosis were imaged at 4.7T using three‐dimensional (3D) susceptibility‐weighted imaging (SWI) with 0.90 mm³ voxel volumes, and with 2D T2‐weighted fast spin echo (T2WFSE) with 0.34 mm³ voxels and 1.84 mm³ voxels. The visibility of MS lesions at 4.7T with phase SWI and T2WFSE was assessed by independent lesion counts made by an experienced neuroradiologist, and by quantitative measures.

Results

High resolution T2WFSE at 4.7T provided excellent depiction of hyperintense lesions. When combined with phase SWI, 124 total lesions were identified of which 18% were only visible on phase SWI and not on T2WFSE. The phase lesions had a mean phase shift relative to local background of ?11.15 ± 5.97 parts per billion.

Conclusion

Imaging at 4.7T can provide both high quality, high resolution T2WFSE and SWI for visualization of lesions in multiple sclerosis. Phase susceptibility‐weighting can identify additional lesions that are not visible with high resolution T2WFSE. J. Magn. Reson. Imaging 2009;30:737–742. © 2009 Wiley‐Liss, Inc.

     

Combined use of T2‐weighted MRI and T1‐weighted dynamic contrast–enhanced MRI in the automated analysis of breast lesions

A multiparametric computer‐aided diagnosis scheme that combines information from T₁‐weighted dynamic contrast–enhanced (DCE)‐MRI and T₂‐weighted MRI was investigated using a database of 110 malignant and 86 benign breast lesions. Automatic lesion segmentation was performed, and three categories of lesion features (geometric, T₁‐weighted DCE, and T₂‐weighted) were automatically extracted. Stepwise feature selection was performed considering only geometric features, only T₁‐weighted DCE features, only T₂‐weighted features, and all features. Features were merged with Bayesian artificial neural networks, and diagnostic performance was evaluated by ROC analysis. With leave‐one‐lesion‐out cross‐validation, an area under the ROC curve value of 0.77 ± 0.03 was achieved with T₂‐weighted‐only features, indicating high diagnostic value of information in T₂‐weighted images. Area under the ROC curve values of 0.79 ± 0.03 and 0.80 ± 0.03 were obtained for geometric‐only features and T₁‐weighted DCE‐only features, respectively. When all features were considered, an area under the ROC curve value of 0.85 ± 0.03 was achieved. We observed P values of 0.006, 0.023, and 0.0014 between the geometric‐only, T₁‐weighted DCE‐only, and T₂‐weighted‐only features and all features conditions, respectively. When ranked, the P values satisfied the Holm–Bonferroni multiple‐comparison test; thus, the improvement of multiparametric computer‐aided diagnosis was statistically significant. A computer‐aided diagnosis scheme that combines information from T₁‐weighted DCE and T₂‐weighted MRI may be advantageous over conventional T₁‐weighted DCE‐MRI computer‐aided diagnosis. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

Free‐breathing diffusion‐weighted imaging for the assessment of inflammatory activity in Crohn's disease

Purpose

To investigate the application of free‐breathing diffusion‐weighted MR imaging (DWI) to the assessment of disease activity in Crohn's disease.

Materials and Methods

Thirty‐one patients with Crohn's disease were investigated using free‐breathing DWI without special patient preparation or IV or intraluminal contrast agent. The bowel was divided into seven segments, and disease activity was assessed visually on DWI. For quantitative analysis, the apparent diffusion coefficient (ADC) was measured in each segment. The findings of a conventional barium study or surgery were regarded as the gold standard for evaluating the diagnostic ability of DWI to assess disease activity.

Results

Upon visual assessment, the sensitivity, specificity, and accuracy for the detection of disease‐active segments were 86.0, 81.4, and 82.4%, respectively. In the quantitative assessment, the ADC value in the disease‐active area was lower than that in disease‐inactive area in small and large bowels (1.61 ± 0.44×10^?3 mm²/s versus 2.56 ± 0.51 × 10^?3 mm²/s in small bowel and 1.52 ± 0.43 × 10^?3 mm²/s versus 2.31 ± 0.59 × 10^?3 mm²/s in large bowel, respectively, P<0.001).

Conclusion

Free‐breathing DWI is useful in the assessment of Crohn's disease. The accuracy of DWI is high in evaluating disease activity, especially in the small bowel, and the ADC may facilitate quantitative analysis of disease activity. J. Magn. Reson. Imaging 2009;29:880–886. © 2009 Wiley‐Liss, Inc.

     

MR susceptibility weighted imaging (SWI) complements conventional contrast enhanced T1 weighted MRI in characterizing brain abnormalities of Sturge-Weber Syndrome

PURPOSE: To evaluate the efficacy of susceptibility weighted imaging (SWI) in comparison to standard T1 weighted postgadolinium contrast (T1-Gd) MRI in patients with Sturge-Weber Syndrome (SWS). MATERIALS AND METHODS: Twelve children (mean age, 5.6 years) with the diagnosis of SWS and unilateral hemispheric involvement were recruited prospectively and examined with high resolution three dimensional SWI and conventional T1-Gd. Both SWI and T1-Gd images were evaluated using a four-grade scoring system according to six types of imaging findings (enlargement of transmedullary veins, periventricular veins, and choroid plexus, as well as leptomeningeal abnormality, cortical gyriform abnormality, and gray matter/white matter junctional abnormality). The scores of SWI versus T1-Gd images were then compared for each type of abnormality. RESULTS: SWI was superior to T1-Gd in identifying the enlarged transmedullary veins (P = 0.0020), abnormal periventricular veins (P = 0.0078), cortical gyriform abnormalities (P = 0.0020), and gray matter/white matter junction abnormalities (P = 0.0078). Conversely, T1-Gd was better than SWI in identifying enlarged choroid plexus (P = 0.0050) and leptomeningeal abnormalities (P = 0.0050). CONCLUSION: SWI can provide useful and unique information complementary to conventional contrast enhanced T1 weighted MRI for characterizing SWS. Therefore, SWI should be integrated into routine clinical MRI protocols for suspected SWS.     

Removing background phase variations in susceptibility‐weighted imaging using a fast,forward‐field calculation

Purpose

To estimate magnetic field variations induced from air–tissue interface geometry and remove their effects from susceptibility‐weighted imaging (SWI) data.

Materials and Methods

A Fourier transform–based field estimation method is used to calculate the field deviation arising from air–tissue interface geometry. This is accomplished by manually drawing or automatically detecting the sinuses, the mastoid cavity, and the head geometry. The difference in susceptibility, Δχ, between brain tissue and air spaces is then calculated using a residual‐phase minimization approach. SWI data are corrected by subtracting the predicted phase from the original phase images. Resultant phase images are then used to perform the SWI postprocessing.

Results

Significant improvement in the postprocessed SWI data is demonstrated, most notably in the frontal and midbrain regions and to a lesser extent at the boundary of the brain. Specifically, there is much less dropout of signal after phase correction near air–tissue interfaces, making it possible to see vessels and structures that were often incorrectly removed by the conventional SWI postprocessing.

Conclusion

The Fourier transform–based field estimation method is a powerful 3D background phase removal method for improving SWI images, providing clearer images of the forebrain and the midbrain regions. J. Magn. Reson. Imaging 2009;29:937–948. © 2009 Wiley‐Liss, Inc.     

Diffusion‐weighted MRI in Crohn's disease: Current status and recommendations

Over the past years, technological improvements and refinements in magnetic resonance imaging (MRI) hardware have made high‐quality diffusion‐weighted imaging (DWI) routinely possible for the bowel. DWI is promising for the detection and characterization of lesions in Crohn's disease (CD) and has been advocated as an alternative to intravenous gadolinium‐based contrast agents. Furthermore, quantification using the apparent diffusion coefficient may have value as a biomarker of CD activity and has shown promise. In this article we critically review the literature pertaining to the value of DWI in CD for detection, characterization, and quantification of disease activity and complications. Although the body of supportive evidence is growing, it is clear that well‐designed, multicenter studies are required before the role of DWI in clinical practice can be fully established. J. Magn. Reson. Imaging 2016;44:1381–1396.