High Spectral And Spatial Resolution Research Articles

High spectral and spatial resolution MRI of age‐related changes in murine prostate

The purpose of this work was to evaluate high-resolution echo-planar spectroscopic MRI of normal and precancerous prostatic changes in a transgenic mouse line. Simian virus large T-antigen transgenic male mice (N = 7, age = 34 +/- 3.7 weeks) with prostatic hyperplasia and intraepithelial neoplasia (PIN) were studied. High spectral and spatial resolution (HiSS) MRI of the water proton signal was compared to the free induction decay (FID) integral image and conventional gradient-echo and spin-echo imaging. Water peak-height images of the prostate produced from HiSS datasets showed improved contrast-to-noise ratio (CNR) (P < 0.03), and greater morphological detail (P < 0.004) based on texture analysis. Despite the high spectral resolution of the HiSS datasets, signal-to-noise ratio (SNR) compared favorably with that of the FID integral and conventional images. Lobular features in HiSS images of older mice were consistent with hyperplasia seen on histology. A partially deuterated water-filled catheter was inserted in the mouse rectum for susceptibility matching between the colon interior and exterior to minimize image artifacts. These preliminary results suggest that HiSS MRI provides detailed morphology of the murine prostate and can detect early changes associated with the development of cancer. HiSS MRI of patients may have similar advantages.

Quantitative analysis of water proton spectral lineshape: a novel source of contrast in MRI

Previous work in this laboratory has demonstrated improved anatomic and functional images produced from high spectral and spatial resolution (HiSS) MRI of the water proton signal. The present work tests the hypothesis that different Fourier components of the water resonance represent anatomically and/or physiologically distinct populations of water molecules within each small image voxel. HiSS datasets were acquired from tomatoes and rodent tumors at 4.7 T using echo-planar spectroscopic imaging (spatial and spectral resolutions were 117–150 µm and 1.5–3.1 Hz, respectively). Images of each Fourier component of the water resonance (referred to as Fourier component images, or FCIs) were produced. FCIs at frequencies offset from the peak of the water resonance (‘off-peak’ FCIs) were compared to images of the Fourier component with largest amplitude, i.e. the water peak-height image. Results demonstrate that off-peak FCIs differ significantly from the water peak-height image and that water resonances are often asymmetric. These results show that water signal at various frequency offsets from the peak of the water resonance come from water molecules in different anatomic/physiologic environments. Off-peak FCIs are a new source of structural and functional information and may have clinical utility.

Fat suppression with spectrally selective inversion vs. high spectral and spatial resolution MRI of breast lesions: Qualitative and quantitative comparisons

To compare conventional fat-suppressed MR images of the breast to images derived from high spectral and spatial resolution MR data. Image quality and the level of fat suppression are compared qualitatively and quantitatively. Women with suspicious breast lesions found on X-ray mammography were imaged on 1.5 Tesla GE SIGNA scanners. High spectral and spatial resolution (HiSS) data were acquired using echo-planar spectroscopic imaging. Images with intensity proportional to the water signal peak height in each voxel were synthesized. Conventional fat-suppressed images were acquired using a frequency selective inversion method. The experimental (HiSS) and conventional images were compared by experienced radiologists to evaluate the quality of fat suppression. In addition, fat suppression and image quality were evaluated quantitatively. Fat suppression, tumor edge delineation, lesion conspicuity, and image texture were improved in the peak height images derived from HiSS data. The results demonstrate that the water peak height images obtained from HiSS data potentially could improve the quality of fat suppression, detection and diagnosis of breast cancer. HiSS allowed detection of lesions and evaluation of lesion morphology prior to contrast media injection. J. Magn. Reson. Imaging 2006. (c) 2006 Wiley-Liss, Inc.

High Spectral and Spatial Resolution MRI of Breast Lesions: Preliminary Clinical Experience

In previous research, high spectral and spatial resolution (HiSS) echo-planar spectroscopic imaging (EPSI) was successfully applied to the human breast, obtaining improved contrast, anatomic detail, and sensitivity to contrast agents. To test HiSS in the clinical setting, we used HiSS MRI to image 30 women with suspicious breast lesions. Women with suspicious breast lesions were scanned before and after contrast administration using EPSI at 1.5 T (0.63-mm in-plane resolution, 2.6-Hz spectral resolution). Images with intensity proportional to the water signal peak height in each voxel were synthesized and compared with standard clinical fat-saturated and early dynamic subtraction images. Pre- and postcontrast HiSS images were compared to assess the effect of the contrast agent on water resonance structure. HiSS images scored significantly better than standard clinical images in lesion conspicuity, margin definition, and internal definition, even though they were acquired before contrast agent injection. Fat suppression was more complete and uniform and detail was shown on HiSS images more clearly than on conventional fat-saturation images. Thus, HiSS images often allowed easier evaluation of the lesion. Contrast agent-affected changes were often spatially and spectrally inhomogeneous. HiSS scans were successfully integrated into standard clinical examinations and provided diagnostically useful images before contrast agent injection. Thus, it might be possible to characterize suspicious lesions on the basis of precontrast high-resolution spectral information. This information and information about the effect of contrast agents could potentially improve the specificity of breast MRI.

High energy heavy ion jets emerging from laser plasma generated by long pulse laser beams from the NHELIX laser system at GSI

High energy heavy ions were generated in laser produced plasma at moderate laser energy, with a large focal spot size of 0.5 mm diameter. The laser beam was provided by the 10 GW GSI-NHELIX laser systems, and the ions were observed spectroscopically in status nascendi with high spatial and spectral resolution. Due to the focal geometry, plasma jet was formed, containing high energy heavy ions. The velocity distribution was measured via an observation of Doppler shifted characteristic transition lines. The observed energy of up to 3 MeV of F-ions deviates by an order of magnitude from the well-known Gitomer (Gitomer et al., 1986) scaling, and agrees with the higher energies of relativistic self focusing.

Comparison of high‐resolution echo‐planar spectroscopic imaging with conventional MR imaging of prostate tumors in mice

High spectral and spatial resolution (HiSS) MRI of rodent tumors has previously been performed using conventional spectroscopic imaging to obtain images with improved contrast and anatomic detail. The work described here evaluates the use of much faster echo-planar spectroscopic imaging (EPSI) to acquire HiSS data from rodent tumor models of prostate cancer. A high-resolution EPSI pulse sequence was implemented on a 4.7 T Bruker scanner. Three-dimensional EPSI data were Fourier-transformed along the k-space and temporal (free-induction decay) axes to produce detailed water and fat spectra associated with each small image voxel. The data were used to generate images of spectral parameters, e.g. peak-height images for each small voxel. Two variants of EPSI were performed; gradient-echo or spin-echo excitation with EPSI readout. These imaging methods were tested in commonly used rodent prostate cancers, including seven mice implanted with non-metastatic AT2.1 (n=3) and metastatic AT3.1 (n=4) prostate tumors on the hind leg, and 10 mice implanted with LNCaP prostate cancers in situ. The peak-height images derived from EPSI datasets provide more detailed tumor anatomy, improved signal-to-noise and contrast-to-noise ratios compared with the gradient-echo or spin-echo images at all echo times. The results suggest that HiSS MRI data from small animal models of prostate cancer can be acquired using EPSI, and that this approach improves imaging of heterogeneous tissue and vascular environments inside the tumors compared with conventional MR techniques.

Fourier components of inhomogeneously broadened water resonances in breast: a new source of MRI contrast.

High spectral and spatial resolution (HiSS) MR data were acquired at 1.5 T using echo-planar spectroscopic imaging from patients with suspicious breast lesions. The water resonances in small voxels are inhomogenously broadened and often have distinct components. Images were calculated with intensity proportional to the Fourier components of the water resonance in each voxel at different offsets from the peak frequency. The results demonstrate that in breast the off-peak Fourier component images of water are qualitatively different from those derived from the peak height of the water resonance. These differences most likely reflect underlying anatomy or physiology. In conventional images, the superposition of the various Fourier components of the water signal may cause loss of detail. The synthesis of water Fourier component images from high spectral and spatial resolution data may provide a new form of contrast, and increase sensitivity to subvoxel physiology and anatomy.

The effect of varying spectral resolution on the quality of high spectral and spatial resolution magnetic resonance images of the breast.

To evaluate the effect of varying spectral resolution on image quality of high spectral and spatial resolution (HiSS) images. Eight women with suspicious breast lesions and six healthy volunteers were scanned using echo-planar spectroscopic imaging (EPSI) at 1.5 Tesla with 0.75- to 1-mm in-plane resolution and 2.3- to 2.6-Hz spectral resolution. Time domain data were truncated to obtain proton spectra in each voxel with varying (2.6-83.3 Hz) resolution. Images with intensity proportional to water signal peak heights were synthesized. Changes in water signal line shape following contrast injection were analyzed. Fat suppression is optimized at approximately 10-Hz spectral resolution and is significantly improved by removal of wings of the fat resonance. This was accomplished by subtracting a Lorentzian fit to the fat resonance from the proton spectrum. The water resonance is often inhomogeneously broadened, and very high spectral resolution is necessary to resolve individual components. High spectral resolution is required for optimal contrast in anatomic features with very high T(2)* (e.g., within a lesion) and for detection of often subtle effects of contrast agents on water signal line shape. Despite a trade-off between the spectral resolution and signal-to-noise ratio, it is beneficial to acquire data at the highest spectral resolution currently attainable at 1.5 Tesla.

Structure of the water resonance in small voxels in rat brain detected with high spectral and spatial resolution MRI.

To acquire high spectral and spatial resolution (HiSS) MR images of the water resonance in rat brain, evaluate the lineshape of the water resonance in small voxels, and compare images derived from HiSS data with conventional images. Spectroscopic images of rat brain were obtained at 4.7 Tesla using phase encoding gradients only. Spectral resolution in each voxel was approximately 8 Hz and bandwidth was 1,000 Hz. Spatial resolution was approximately 250 microns in 1-mm slices. Images were synthesized to show the water signal integral, peak height, linewidth, resonance frequency, and asymmetry. Two or more resolved components of the water resonance were detected in approximately 14% +/- 6% of voxels in the brains of eight rats. The water resonances in approximately 20% +/- 10% of voxels (n = 8) were highly asymmetric. Images with intensity proportional to water signal peak height, T(2)*, or to selected components of the water resonance showed features that were not evident in conventional images. The complexity of the water signal reflects the anatomy and physiology of the sub-voxelar environment, and may be a useful source of image contrast. HiSS imaging of brain provides accurate anatomic information, and may improve image contrast and delineation of subtle anatomic features.

Spectrally Inhomogeneous Effects of Contrast Agents in Breast Lesion Detected by High Spectral and Spatial Resolution MRI

Improvements in MR hardware and software allow acquisition of data at very high spectral and spatial resolution so that the details of the water and fat lineshapes in each small image voxel can be resolved (1). Data obtained with high spectral and spatial resolution (HiSS) MR imaging demonstrate that the water proton resonance in small voxels is complicated, and is frequently composed of multiple well-resolved components (2–5). This inhomogeneous broadening is generally caused by local magnetic susceptibility gradients that reflect local anatomy and physiology. Previous work in this laboratory showed that effects of contrast agents in very small image voxels are often spectrally inhomogeneous (2–5). This reflects effects of the contrast agent in different sub-voxelar, perhaps microscopic environments (2–4). For example, small areas with high angiogenic activity in tumors may be detectable with increased sensitivity in HiSS images, because the water signal from these regions may be slightly shifted relative to the water signal from the rest of the voxel. The purpose of these experiments was to image contrast media uptake in breast lesions using HiSS MRI. MATERIALS AND METHODS

Spectrally inhomogeneous BOLD contrast changes detected in rodent tumors with high spectral and spatial resolution MRI.

MRI detects changes in blood-oxygenation-level dependent (BOLD) contrast in tumors caused by tumor oxygenating agents. These changes can be used to guide the design of improved tumor oxygenating treatments (TOXs). The conventional approach to detection of BOLD effects assumes that the water resonance is a single, homogeneously broadened Lorentzian line, and that changes in the T2* of this line owing to changes in deoxyhemoglobin are spectrally homogeneous. This model may not adequately describe BOLD contrast changes in complex water resonances that are often detected in tumors. The present work investigated: (a) whether changes in the water resonance in very small voxels caused by tumor oxygenating agents are spectrally inhomogeneous; and (b) whether high spectral and spatial resolution (HiSS) MRI of the water and fat resonances detects these changes more accurately than conventional gradient-recalled echo (GRE) imaging. Carbogen (95% oxygen, 5% CO2) was used to increase tumor oxygenation. In two tumor models [mammary adenocarcinoma (R3230Ac; n=5) and rhabdomyosarcoma (BA1112; n=5)] proton signals were often complex and inhomogeneously broadened. Spectrally inhomogeneous changes during carbogen breathing occurred in at least 10% of the R3230AC tumor voxels that responded to carbogen and 18% of BA1112 tumor voxels. The largest changes during carbogen breathing in many voxels occurred at frequencies that were significantly different from the frequency of the primary water peak. Carbogen-induced changes in proton T2* detected by simulated GRE and HiSS differed by more than 75% in 67% of voxels in R3230Ac tumors and in 65% of voxels in BA1112 tumors. The spectrally inhomogeneous effects of tumor oxygenating agents may reflect changes in sub-voxelar microenvironements and thus may be important for accurate evaluation of the effects of therapy.

Functional and Anatomic Imaging of Tumor Vasculature: High-Resolution MR Spectroscopic Imaging Combined with a Superparamagnetic Contrast Agent

The advantages of incorporating spectroscopic information into magnetic resonance imaging (MRI) data sets were demonstrated by Dixon (1) and later by others (2,3). This early work focused on imaging water and fat signals with low spectral resolution combined with high spatial resolution. More recently, improvements in MR instrumentation have encouraged detection of water and fat with both high spatial and spectral resolution (HiSS) MR to improve anatomic detail and contrast (4–8) in tissues with broad and complex water proton resonances. This is particularly important in tumors but may also be applicable to imaging regions in the brain that have been damaged by stroke and other conditions associated with hemorrhage and necrosis. HiSS can improve imaging of the effects of endogenous and injected contrast agents. For example, in this laboratory, HiSS has been used to image changes in deoxyhemoglobin levels in tumors caused by tumor-oxygenating agents and hemodynamic challenges (6,7,9). HiSS is also useful for imaging effects of synthetic contrast agents. The data presented here illustrate the use of HiSS to detect superparamagnetic contrast agents. Superparamagnetic MR contrast agents provide a unique opportunity to detect tumors, define tumor anatomy, delineate tumor boundaries, and evaluate vascular structure and function of tumors. The complexity of the effects of these agents provides new mechanisms for contrast in MR images but also poses a challenge for MRI. Iron oxide particles with small diameters have very large Rl and R2* (longitudinal and transverse relaxivities), and both effects may be spectrally inhomogeneous (ie, different components of the water resonance in each voxel are affected differently). The results presented here suggest that to measure these effects independently, accurately, and with a high signal-to-noise ratio, it is advantageous to acquire spectroscopic images with high spectral and spatial resolution.

Uptake of a superparamagnetic contrast agent imaged by MR with high spectral and spatial resolution.

Conventional MRI implicitly treats the proton signal as a single, narrow Lorentzian. However, water signals in vivo are often in homogeneously broadened and have multiple resolvable components. These components represent discrete populations of water molecules within each pixel which are affected differently by physiology and contrast agents. Accurate measurement of each component of the water resonance can improve anatomic and functional MR images and provide insight into the structure and dynamics of subpixelar microenvironments. This report describes high spectral and spatial resolution (HiSS) MR imaging of rodent prostate tumors before and after injection of a superparamagnetic contrast agent. HiSS datasets were used to synthesize images in which intensity is proportional to peak height, peak frequency, and linewidth. These images showed anatomic features which were not clearly delineated in conventional T(2) and gradient echo images. HiSS images obtained after injection of the contrast agent showed T *(2) and T(1) changes which were not seen in conventional images. These changes are associated with microvessel density and permeability. The results suggest HiSS with superparamagnetic contrast agents has the potential to improve characterization of tumors.

Uptake of a superparamagnetic contrast agent imaged by MR with high spectral and spatial resolution

Conventional MRI implicitly treats the proton signal as a single, narrow Lorentzian. However, water signals in vivo are often inhomogeneously broadened and have multiple resolvable components. These components represent discrete populations of water molecules within each pixel which are affected differently by physiology and contrast agents. Accurate measurement of each component of the water resonance can improve anatomic and functional MR images and provide insight into the structure and dynamics of subpixelar microenvironments. This report describes high spectral and spatial resolution (HiSS) MR imaging of rodent prostate tumors before and after injection of a superparamagnetic contrast agent. HiSS datasets were used to synthesize images in which intensity is proportional to peak height, peak frequency, and linewidth. These images showed anatomic features which were not clearly delineated in conventional T2 and gradient echo images. HiSS images obtained after injection of the contrast agent showed T *2 and T1 changes which were not seen in conventional images. These changes are associated with microvessel density and permeability. The results suggest HiSS with superparamagnetic contrast agents has the potential to improve characterization of tumors. Magn Reson Med 43:633–639, 2000. © 2000 Wiley-Liss, Inc.