In previous research, high spectral and spatial resolution (HiSS) echo-planar spectroscopic imagi... more 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.
Journal of Biological Inorganic Chemistry Jbic a Publication of the Society of Biological Inorganic Chemistry, Jul 2, 2009
We have developed a magnetic resonance imaging (MRI) method for improved detection of cancer with... more We have developed a magnetic resonance imaging (MRI) method for improved detection of cancer with a new class of cancer-specific contrast agents, containing vanadyl (VO 2? )-chelated organic ligands, specifically bis(acetylacetonato)oxovanadium(IV) [VO(acac) 2 ]. Vanadyl compounds have been found to accumulate within cells, where they interact with intracellular glycolytic enzymes. Aggressive cancers are metabolically active and highly glycolytic; an MRI contrast agent that enters cells with high glycolytic activity could provide high-resolution functional images of tumor boundaries and internal structure, which cannot be achieved by conventional contrast agents. The present work demonstrates properties of VO(acac) 2 that may give it excellent specificity for cancer detection. A high dose of VO(acac) 2 did not cause any acute or short-term adverse reactions in murine subjects. Calorimetry and spectrofluorometric methods demonstrate that VO(acac) 2 is a blood pool agent that binds to serum albumin with a dissociation constant K d * 2.5 ± 0.7 9 10 -7 M and a binding stoichiometry n = 1.03 ± 0.04. Owing to its prolonged blood half-life and selective leakage from hyperpermeable tumor vasculature, a low dose of VO(acac) 2 (0.15 mmol/kg) selectively enhanced in vivo magnetic resonance images of tumors, providing highresolution images of their interior structure. The kinetics of uptake and washout are consistent with the hypothesis that VO(acac) 2 preferentially accumulates in cancer cells. Although VO(acac) 2 has a lower relaxivity than gadolinium-based MRI contrast agents, its specificity for highly glycolytic cells may lead to an innovative approach to cancer detection since it has the potential to produce MRI contrast agents that are nontoxic and highly sensitive to cancer metabolism.
The authors evaluated magnetic resonance (MR) imaging with high spectral and spatial resolutions ... more The authors evaluated magnetic resonance (MR) imaging with high spectral and spatial resolutions (HSSR) of water and fat in breasts of healthy volunteers (n = 6) and women with suspicious lesions (n = 6). Fat suppression, edge delineation, and image texture were improved on MR images derived from HSSR data compared with those on conventional MR images. HSSR MR imaging data acquired before and after contrast medium injection showed spectrally inhomogeneous changes in the water resonances in small voxels that were not detectable with conventional MR imaging.
MR images can be acquired with high spectral and spatial resolution to precisely measure lineshap... more MR images can be acquired with high spectral and spatial resolution to precisely measure lineshapes of the water and fat resonances in each image voxel. Previous work suggests that the high-resolution spectral information can be used to improve image contrast, SNR, sensitivity to contrast agents and to physiologic and biochemical processes that affect local magnetic susceptibility gradients. The potential advantages of high-resolution spectroscopic imaging (SI) suggest that it might be useful for early detection and characterization of tumors. The present experiments evaluate the use of high-resolution SI to discriminate between metastatic and nonmetastatic rodent Dunning prostate tumors. SI datasets were obtained at 4.7 Tesla with an in-plane resolution of 350 -500 in a single 1.0-mm slice, and 6 -8 Hz spectral resolution, before and after i.v. injection of an iron oxide contrast agent. Images of water signal peak height in nonmetastatic tumors were smoother in the tumor interior than images of metastatic tumors (P < .004 by t-test) before contrast media injection. This difference was stronger in contrast-enhanced images (P < .0004). In addition, the boundary between the tumor and muscle was more clearly demarcated in nonmetastatic than metastatic tumors. Combinations of image texture, tumor edge morphology, and changes in T * 2 following contrast media injection improved discrimination between metastatic and nonmetastatic tumors. The data presented here do not demonstrate that effective discrimination between metastatic and nonmetastatic tumors depends on the use of high-resolution SI. However, the results suggest that SI and/or other MR methods that provide similar contrast might be used clinically for early and accurate detection of metastatic disease. Magn Reson Med 45:1046 -1055, 2001.
High spectral and spatial resolution (HiSS) MR imaging has been used to improve the quality of an... more High spectral and spatial resolution (HiSS) MR imaging has been used to improve the quality of anatomic and functional images. HiSS datasets provide detailed water and fat spectra associated with each voxel. In many voxels, distinct components of the water and fat lineshapes can be identified. Here we demonstrate that in breast, the different Fourier components of the water resonance and the fat resonance give rise to qualitatively different images. Introduction: High spectral and spatial resolution (HiSS) imaging in various forms has been used to improve the quality of anatomic and functional imaging (1-3). HiSS datasets from the breast provide a detailed water and fat spectrum associated with each small image voxel. These data demonstrate that water and fat resonances in small voxels are often inhomogeneously broadened (3,4). It is likely that the different components of water and fat signals come from distinct subvoxel environments and reflect local anatomy and physiology. Here, we demonstrate that in human breast the different Fourier components of the water and fat resonances from very small voxels give rise to images with significantly different features. Methods: HiSS data were acquired from women with suspicious breast lesions or normal breasts at 1.5 Tesla. Inplane spatial resolution was ~750 microns in 3 mm thick slices, and spectral resolution was ~2.6 Hz. Signals from water (or fat) in each image voxel were shifted so that the peak of the water (or fat) resonance was at the same resonance frequency in all voxels. Then images were calculated with intensity proportional to the Fourier components of the water (or fat) resonance at different offsets from the peak frequency. Results: FCIs (Fourier component images) often contained distinct anatomic features. For example, shows FCI's acquired from a patient with infiltrating ductal carcinoma. The images are labeled with the corresponding frequency offset from the main peak. The FCI at -21 Hz shows a bright elongated area in the upper right quadrant of the lesion. A small bright area near the lesion center is clearly depicted in the 16 Hz image but not at the other frequencies. The texture at 0 Hz is relatively smooth with a few dark lines, while at 10 Hz and 16 Hz there is a more complicated pattern of bright and dark lines, perhaps arising from vasculature. Many features that are prominent in the FCI at 0 Hz have a narrow bandwidth and are not detectable in other FCI's. Discussion: It is reasonable to suggest that different Fourier components of the water resonance produce different images because they arise from different components of the subvoxel environment. As a result each Fourier component represents a particular aspect of the anatomy and physiology within each voxel. Thus HiSS MRI may increase sensitivity to details of the subvoxel environment. This is a novel contrast mechanism and may yield information that cannot be duplicated with other methods of contrast enhancement.
PURPOSE To evaluate the application of high spectral and spatial resolution (HiSS) MR imaging and... more PURPOSE To evaluate the application of high spectral and spatial resolution (HiSS) MR imaging and compare HiSS images to standard clinical breast MR images in patients with suspected breast carcinoma. METHOD AND MATERIALS Thirty eight patients were imaged after informed consent was obtained. All patients had clinical and/or conventional imaging findings suggestive of carcinoma. Conventional pre- and post- infusion breast MR images were acquired with a bilateral breast coil, including axial T2-weighted FSE, pre and post infusion dynamic T1-weighted SPGR, and sagittal T1-weighted SPGR fat-saturated images. Additional HiSS scans (either one 4 mm or two 3 mm (n=3) slices in previously selected area of interest) were added before and at 3.5 minutes after contrast media injection. HiSS data were acquired using echo-planar spectroscopic imaging with sub-millimeter spatial resolution and with high-resolution (2.6 � 5.2 Hz) spectra of water and fat resonances associated with each image voxel...
PURPOSE Use MRI to evaluate progression of transplanted rodent prostate cancers in control rats a... more PURPOSE Use MRI to evaluate progression of transplanted rodent prostate cancers in control rats and rats treated with green tea. METHOD AND MATERIALS AT6.1 metastatic rodent prostate cancer cells were implanted in the hind limbs of Copenhagen rats. Animals were assigned randomly to a control (drinking water) or treated (drinking green tea) group after the first MRI scan (Week 0). Control and treated rats were imaged 7 days (Week 1) and 14 days (Week 2) after the first scan. Dynamic contrast enhanced MR images were acquired pre- and post I.V. injection of Gd-DTPA, on a 4.7 Tesla animal imaging scanner. The ‘two-compartment model’ was used to analyze the data on a pixel-by-pixel basis to obtain the volume transfer constant (Ktrans) between blood plasma and the extravascular extracellular space (EES), and the volume of EES per unit volume of tissue (ve). Tumor growth rate was also determined based on the volumetric MRI measurements using an exponential model. RESULTS The shape of histo...
Introduction: BOLD MRI is often used to evaluate effects of oxygenating agents in tumors. A gradi... more Introduction: BOLD MRI is often used to evaluate effects of oxygenating agents in tumors. A gradient echo with long TE or a train of several gradient echoes is often used to detect changes in T 2 * reflecting changes in blood oxygenation. However, this approach leads to artifacts and loss of sensitivity when the water resonance does not behave as a homogeneously broadened Lorentzian line. The water resonance from small voxels in vivo is usually inhomogeneously broadened, and the various components of the water resonance often respond differently to changes in oxygenation. Here we demonstrate that with high resolution EPSI, changes in each individual Fourier component of the water resonance during carbogen breathing can be imaged. Further, we show that examination of these Fourier component images reveal BOLD changes that are missed by conventional imaging. Method: Nude mice (n = 5) were inoculated in the hind leg with AT6.1 tumor cells. EPSI was performed using a 4.7T scanner with 1...
Dynamic contrast-enhanced MRI (DCE-MRI) has become a standard component of multiparametric protoc... more Dynamic contrast-enhanced MRI (DCE-MRI) has become a standard component of multiparametric protocols for MRI examination of the prostate, and its use is incorporated into current guidelines for prostate MRI examination. Analysis of DCE-MRI data for the prostate is usually based on the distribution of gadolinium-based agents, such as gadodiamide, into two well-mixed compartments, and it assumes that gadodiamide does not enter into the glandular lumen. However, this assumption has not been directly tested. The purpose of this study was to use x-ray fluorescence microscopy (XFM) imaging in situ to measure the concentration of gadodiamide in the epithelia and lumens of the prostate of healthy mice after IV injection of the contrast agent. Six C57Bl6 male mice (age, 28 weeks) were sacrificed 10 minutes after IV injection of gadodiamide (0.13 mmol/kg), and three mice were sacrificed after saline injection. Prostate tissue samples obtained from each mouse were harvested and frozen; 7-μm-thick slices were sectioned for XFM imaging, and adjacent 5-μm-thick slices were sectioned for H and E staining. Elemental concentrations were determined from XFM images. A mean (± SD) baseline concentration of gadolinium of 0.01 ± 0.01 mM was determined from XFM measurements of prostatic tissue samples when no gadodiamide was administered, and it was used to determine the measurement error. When gadodiamide was added, the mean concentrations of gadolinium in the epithelia and lumens in 32 prostatic glands from six mice were 1.00 ± 0.13 and 0.36 ± 0.09 mM, respectively. Our data suggest that IV administration of gadodiamide results in uptake of contrast agent by the glandular lumens of the mouse prostate. We were able to quantitatively determine gadodiamide distributions in mouse prostatic epithelia and lumens.
Proceedings of the 22nd Annual International Conference of the IEEE Engineering in Medicine and Biology Society (Cat. No.00CH37143), 2000
MR signals can be acquired with high spatial and spectral resolution so that each pixel is repres... more MR signals can be acquired with high spatial and spectral resolution so that each pixel is represented by a high-resolution proton spectrum of water and fat. The spectra can be analyzed to produce images with improved contrast, anatomic accuracy, and sensitivity to contrast media uptake, compared to conventional MR imaging. Analysis of high spectral and spatial resolution (HiSS) MR datasets
Ex vivo MRI may aid in the evaluation of surgical specimens, and provide valuable information reg... more Ex vivo MRI may aid in the evaluation of surgical specimens, and provide valuable information regarding the micro-anatomy of mammary/breast cancer. The use of ex vivo MRI to study mouse mammary cancer would be enhanced if there is a strong correlation between parameters derived from in vivo and ex vivo scans. Here, we report the correlation between apparent diffusion coefficient (ADC) and T2 values measured in vivo and ex vivo in mouse mammary glands with in situ cancers (mammary intraepithelial neoplasia (MIN)) and invasive cancers (those which spread outside the ducts into surrounding tissue). MRI experiments were performed on the Polyoma middle T oncoprotein breast cancer mouse model (n = 15) in a 9.4T scanner. For in vivo experiments, T2-weighted (T2W) images were acquired to identify abnormal regions, then ADC and T2 values were measured for nine selected slices. For ex vivo experiments, a midline incision was made along the spine, and then skin, glands, and tumors were gently peeled from the body. Tissue was fixed in formalin, placed around a mouse-sized sponge, and sutured together mimicking the geometry of the gland when attached to the mouse. The same pulse sequences used for in vivo experiments were repeated for ex vivo scans at room temperature. Regions of interest were manually traced on T2W images defining features that could be identified on in vivo and ex vivo images. The results demonstrate a strong positive correlations between in vivo and ex vivo invasive cancers for ADC (r = 0.89, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001) and T2 (r = 0.89, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001) values; and weak to moderate positive correlations between in vivo and ex vivo in situ cancers for ADC (r = 0.61, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001) and T2 (r = 0.79, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001) values. The average ex vivo ADC value was about 54% of the in vivo value; and the average ex vivo T2 was similar to the in vivo value for cancers. Although motion, fixation, and temperature differences affect ADC and T2, these results show a reliable relationship between ADC and T2 in vivo and ex vivo. As a result ex vivo images can provide valuable information with clinical and research applications.
Advances in experimental medicine and biology, 2003
We evaluate whether high spectral and spatial resolution (HiSS) BOLD MRI can correctly rank the e... more We evaluate whether high spectral and spatial resolution (HiSS) BOLD MRI can correctly rank the effects of three tumor-oxygenating treatments on radiosensitivity in BA1112 rhabdomyosarcomas (n = 5). Significant decreases in spectral linewidth predict that treatment with carbogen gas combined with a perfluorocarbon emulsion will increase radiosensitivity more than either treatment alone, which agrees with the known effects of these treatments on hypoxic fraction. High-resolution maps show that tumor response to each treatment is spatially heterogeneous, and that there is a paradoxical response to the treatments in 7-12% of tumor pixels. Because HiSS MRI emphasizes changes in necrotic and/or hemorrhagic regions, it is more sensitive to oxygenation changes compared to conventional MRI. These results demonstrate that HiSS MRI is a practical, noninvasive method that could be used to choose the treatment that maximizes the size and extent of increases in tumor oxygenation for individual p...
High spectral and spatial resolution (HiSS) MR data were acquired at 1.5 T using echo-planar spec... more 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.
High spectral and spatial resolution (HiSS) data, acquired with echo-planar spectroscopic imaging... more High spectral and spatial resolution (HiSS) data, acquired with echo-planar spectroscopic imaging (EPSI), can be used to acquire water spectra from each small image voxel. These images are sensitive to changes in local susceptibility caused by superparamagnetic iron oxide particles (SPIO); therefore, we hypothesized that images derived from HiSS data are very sensitive to tumor neovasculature following injection of SPIO. Accurate image registration was used to validate HiSS detection of neovasculature with histology and micro-computed tomographic (microCT) angiography. Athymic nude mice and Copenhagen rats were inoculated with Dunning AT6.1 prostate tumor cells in the right hind limb. The tumor region was imaged pre- and post-intravenous injection of SPIO. Three-dimensional assemblies of the CD31-stained histologic slices of the mouse legs and the microCT images of the rat vascular casts were registered with EPSI. The average distance between HiSS-predicted regions of high vascular ...
In previous research, high spectral and spatial resolution (HiSS) echo-planar spectroscopic imagi... more 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.
Journal of Biological Inorganic Chemistry Jbic a Publication of the Society of Biological Inorganic Chemistry, Jul 2, 2009
We have developed a magnetic resonance imaging (MRI) method for improved detection of cancer with... more We have developed a magnetic resonance imaging (MRI) method for improved detection of cancer with a new class of cancer-specific contrast agents, containing vanadyl (VO 2? )-chelated organic ligands, specifically bis(acetylacetonato)oxovanadium(IV) [VO(acac) 2 ]. Vanadyl compounds have been found to accumulate within cells, where they interact with intracellular glycolytic enzymes. Aggressive cancers are metabolically active and highly glycolytic; an MRI contrast agent that enters cells with high glycolytic activity could provide high-resolution functional images of tumor boundaries and internal structure, which cannot be achieved by conventional contrast agents. The present work demonstrates properties of VO(acac) 2 that may give it excellent specificity for cancer detection. A high dose of VO(acac) 2 did not cause any acute or short-term adverse reactions in murine subjects. Calorimetry and spectrofluorometric methods demonstrate that VO(acac) 2 is a blood pool agent that binds to serum albumin with a dissociation constant K d * 2.5 ± 0.7 9 10 -7 M and a binding stoichiometry n = 1.03 ± 0.04. Owing to its prolonged blood half-life and selective leakage from hyperpermeable tumor vasculature, a low dose of VO(acac) 2 (0.15 mmol/kg) selectively enhanced in vivo magnetic resonance images of tumors, providing highresolution images of their interior structure. The kinetics of uptake and washout are consistent with the hypothesis that VO(acac) 2 preferentially accumulates in cancer cells. Although VO(acac) 2 has a lower relaxivity than gadolinium-based MRI contrast agents, its specificity for highly glycolytic cells may lead to an innovative approach to cancer detection since it has the potential to produce MRI contrast agents that are nontoxic and highly sensitive to cancer metabolism.
The authors evaluated magnetic resonance (MR) imaging with high spectral and spatial resolutions ... more The authors evaluated magnetic resonance (MR) imaging with high spectral and spatial resolutions (HSSR) of water and fat in breasts of healthy volunteers (n = 6) and women with suspicious lesions (n = 6). Fat suppression, edge delineation, and image texture were improved on MR images derived from HSSR data compared with those on conventional MR images. HSSR MR imaging data acquired before and after contrast medium injection showed spectrally inhomogeneous changes in the water resonances in small voxels that were not detectable with conventional MR imaging.
MR images can be acquired with high spectral and spatial resolution to precisely measure lineshap... more MR images can be acquired with high spectral and spatial resolution to precisely measure lineshapes of the water and fat resonances in each image voxel. Previous work suggests that the high-resolution spectral information can be used to improve image contrast, SNR, sensitivity to contrast agents and to physiologic and biochemical processes that affect local magnetic susceptibility gradients. The potential advantages of high-resolution spectroscopic imaging (SI) suggest that it might be useful for early detection and characterization of tumors. The present experiments evaluate the use of high-resolution SI to discriminate between metastatic and nonmetastatic rodent Dunning prostate tumors. SI datasets were obtained at 4.7 Tesla with an in-plane resolution of 350 -500 in a single 1.0-mm slice, and 6 -8 Hz spectral resolution, before and after i.v. injection of an iron oxide contrast agent. Images of water signal peak height in nonmetastatic tumors were smoother in the tumor interior than images of metastatic tumors (P < .004 by t-test) before contrast media injection. This difference was stronger in contrast-enhanced images (P < .0004). In addition, the boundary between the tumor and muscle was more clearly demarcated in nonmetastatic than metastatic tumors. Combinations of image texture, tumor edge morphology, and changes in T * 2 following contrast media injection improved discrimination between metastatic and nonmetastatic tumors. The data presented here do not demonstrate that effective discrimination between metastatic and nonmetastatic tumors depends on the use of high-resolution SI. However, the results suggest that SI and/or other MR methods that provide similar contrast might be used clinically for early and accurate detection of metastatic disease. Magn Reson Med 45:1046 -1055, 2001.
High spectral and spatial resolution (HiSS) MR imaging has been used to improve the quality of an... more High spectral and spatial resolution (HiSS) MR imaging has been used to improve the quality of anatomic and functional images. HiSS datasets provide detailed water and fat spectra associated with each voxel. In many voxels, distinct components of the water and fat lineshapes can be identified. Here we demonstrate that in breast, the different Fourier components of the water resonance and the fat resonance give rise to qualitatively different images. Introduction: High spectral and spatial resolution (HiSS) imaging in various forms has been used to improve the quality of anatomic and functional imaging (1-3). HiSS datasets from the breast provide a detailed water and fat spectrum associated with each small image voxel. These data demonstrate that water and fat resonances in small voxels are often inhomogeneously broadened (3,4). It is likely that the different components of water and fat signals come from distinct subvoxel environments and reflect local anatomy and physiology. Here, we demonstrate that in human breast the different Fourier components of the water and fat resonances from very small voxels give rise to images with significantly different features. Methods: HiSS data were acquired from women with suspicious breast lesions or normal breasts at 1.5 Tesla. Inplane spatial resolution was ~750 microns in 3 mm thick slices, and spectral resolution was ~2.6 Hz. Signals from water (or fat) in each image voxel were shifted so that the peak of the water (or fat) resonance was at the same resonance frequency in all voxels. Then images were calculated with intensity proportional to the Fourier components of the water (or fat) resonance at different offsets from the peak frequency. Results: FCIs (Fourier component images) often contained distinct anatomic features. For example, shows FCI's acquired from a patient with infiltrating ductal carcinoma. The images are labeled with the corresponding frequency offset from the main peak. The FCI at -21 Hz shows a bright elongated area in the upper right quadrant of the lesion. A small bright area near the lesion center is clearly depicted in the 16 Hz image but not at the other frequencies. The texture at 0 Hz is relatively smooth with a few dark lines, while at 10 Hz and 16 Hz there is a more complicated pattern of bright and dark lines, perhaps arising from vasculature. Many features that are prominent in the FCI at 0 Hz have a narrow bandwidth and are not detectable in other FCI's. Discussion: It is reasonable to suggest that different Fourier components of the water resonance produce different images because they arise from different components of the subvoxel environment. As a result each Fourier component represents a particular aspect of the anatomy and physiology within each voxel. Thus HiSS MRI may increase sensitivity to details of the subvoxel environment. This is a novel contrast mechanism and may yield information that cannot be duplicated with other methods of contrast enhancement.
PURPOSE To evaluate the application of high spectral and spatial resolution (HiSS) MR imaging and... more PURPOSE To evaluate the application of high spectral and spatial resolution (HiSS) MR imaging and compare HiSS images to standard clinical breast MR images in patients with suspected breast carcinoma. METHOD AND MATERIALS Thirty eight patients were imaged after informed consent was obtained. All patients had clinical and/or conventional imaging findings suggestive of carcinoma. Conventional pre- and post- infusion breast MR images were acquired with a bilateral breast coil, including axial T2-weighted FSE, pre and post infusion dynamic T1-weighted SPGR, and sagittal T1-weighted SPGR fat-saturated images. Additional HiSS scans (either one 4 mm or two 3 mm (n=3) slices in previously selected area of interest) were added before and at 3.5 minutes after contrast media injection. HiSS data were acquired using echo-planar spectroscopic imaging with sub-millimeter spatial resolution and with high-resolution (2.6 � 5.2 Hz) spectra of water and fat resonances associated with each image voxel...
PURPOSE Use MRI to evaluate progression of transplanted rodent prostate cancers in control rats a... more PURPOSE Use MRI to evaluate progression of transplanted rodent prostate cancers in control rats and rats treated with green tea. METHOD AND MATERIALS AT6.1 metastatic rodent prostate cancer cells were implanted in the hind limbs of Copenhagen rats. Animals were assigned randomly to a control (drinking water) or treated (drinking green tea) group after the first MRI scan (Week 0). Control and treated rats were imaged 7 days (Week 1) and 14 days (Week 2) after the first scan. Dynamic contrast enhanced MR images were acquired pre- and post I.V. injection of Gd-DTPA, on a 4.7 Tesla animal imaging scanner. The ‘two-compartment model’ was used to analyze the data on a pixel-by-pixel basis to obtain the volume transfer constant (Ktrans) between blood plasma and the extravascular extracellular space (EES), and the volume of EES per unit volume of tissue (ve). Tumor growth rate was also determined based on the volumetric MRI measurements using an exponential model. RESULTS The shape of histo...
Introduction: BOLD MRI is often used to evaluate effects of oxygenating agents in tumors. A gradi... more Introduction: BOLD MRI is often used to evaluate effects of oxygenating agents in tumors. A gradient echo with long TE or a train of several gradient echoes is often used to detect changes in T 2 * reflecting changes in blood oxygenation. However, this approach leads to artifacts and loss of sensitivity when the water resonance does not behave as a homogeneously broadened Lorentzian line. The water resonance from small voxels in vivo is usually inhomogeneously broadened, and the various components of the water resonance often respond differently to changes in oxygenation. Here we demonstrate that with high resolution EPSI, changes in each individual Fourier component of the water resonance during carbogen breathing can be imaged. Further, we show that examination of these Fourier component images reveal BOLD changes that are missed by conventional imaging. Method: Nude mice (n = 5) were inoculated in the hind leg with AT6.1 tumor cells. EPSI was performed using a 4.7T scanner with 1...
Dynamic contrast-enhanced MRI (DCE-MRI) has become a standard component of multiparametric protoc... more Dynamic contrast-enhanced MRI (DCE-MRI) has become a standard component of multiparametric protocols for MRI examination of the prostate, and its use is incorporated into current guidelines for prostate MRI examination. Analysis of DCE-MRI data for the prostate is usually based on the distribution of gadolinium-based agents, such as gadodiamide, into two well-mixed compartments, and it assumes that gadodiamide does not enter into the glandular lumen. However, this assumption has not been directly tested. The purpose of this study was to use x-ray fluorescence microscopy (XFM) imaging in situ to measure the concentration of gadodiamide in the epithelia and lumens of the prostate of healthy mice after IV injection of the contrast agent. Six C57Bl6 male mice (age, 28 weeks) were sacrificed 10 minutes after IV injection of gadodiamide (0.13 mmol/kg), and three mice were sacrificed after saline injection. Prostate tissue samples obtained from each mouse were harvested and frozen; 7-μm-thick slices were sectioned for XFM imaging, and adjacent 5-μm-thick slices were sectioned for H and E staining. Elemental concentrations were determined from XFM images. A mean (± SD) baseline concentration of gadolinium of 0.01 ± 0.01 mM was determined from XFM measurements of prostatic tissue samples when no gadodiamide was administered, and it was used to determine the measurement error. When gadodiamide was added, the mean concentrations of gadolinium in the epithelia and lumens in 32 prostatic glands from six mice were 1.00 ± 0.13 and 0.36 ± 0.09 mM, respectively. Our data suggest that IV administration of gadodiamide results in uptake of contrast agent by the glandular lumens of the mouse prostate. We were able to quantitatively determine gadodiamide distributions in mouse prostatic epithelia and lumens.
Proceedings of the 22nd Annual International Conference of the IEEE Engineering in Medicine and Biology Society (Cat. No.00CH37143), 2000
MR signals can be acquired with high spatial and spectral resolution so that each pixel is repres... more MR signals can be acquired with high spatial and spectral resolution so that each pixel is represented by a high-resolution proton spectrum of water and fat. The spectra can be analyzed to produce images with improved contrast, anatomic accuracy, and sensitivity to contrast media uptake, compared to conventional MR imaging. Analysis of high spectral and spatial resolution (HiSS) MR datasets
Ex vivo MRI may aid in the evaluation of surgical specimens, and provide valuable information reg... more Ex vivo MRI may aid in the evaluation of surgical specimens, and provide valuable information regarding the micro-anatomy of mammary/breast cancer. The use of ex vivo MRI to study mouse mammary cancer would be enhanced if there is a strong correlation between parameters derived from in vivo and ex vivo scans. Here, we report the correlation between apparent diffusion coefficient (ADC) and T2 values measured in vivo and ex vivo in mouse mammary glands with in situ cancers (mammary intraepithelial neoplasia (MIN)) and invasive cancers (those which spread outside the ducts into surrounding tissue). MRI experiments were performed on the Polyoma middle T oncoprotein breast cancer mouse model (n = 15) in a 9.4T scanner. For in vivo experiments, T2-weighted (T2W) images were acquired to identify abnormal regions, then ADC and T2 values were measured for nine selected slices. For ex vivo experiments, a midline incision was made along the spine, and then skin, glands, and tumors were gently peeled from the body. Tissue was fixed in formalin, placed around a mouse-sized sponge, and sutured together mimicking the geometry of the gland when attached to the mouse. The same pulse sequences used for in vivo experiments were repeated for ex vivo scans at room temperature. Regions of interest were manually traced on T2W images defining features that could be identified on in vivo and ex vivo images. The results demonstrate a strong positive correlations between in vivo and ex vivo invasive cancers for ADC (r = 0.89, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001) and T2 (r = 0.89, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001) values; and weak to moderate positive correlations between in vivo and ex vivo in situ cancers for ADC (r = 0.61, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001) and T2 (r = 0.79, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001) values. The average ex vivo ADC value was about 54% of the in vivo value; and the average ex vivo T2 was similar to the in vivo value for cancers. Although motion, fixation, and temperature differences affect ADC and T2, these results show a reliable relationship between ADC and T2 in vivo and ex vivo. As a result ex vivo images can provide valuable information with clinical and research applications.
Advances in experimental medicine and biology, 2003
We evaluate whether high spectral and spatial resolution (HiSS) BOLD MRI can correctly rank the e... more We evaluate whether high spectral and spatial resolution (HiSS) BOLD MRI can correctly rank the effects of three tumor-oxygenating treatments on radiosensitivity in BA1112 rhabdomyosarcomas (n = 5). Significant decreases in spectral linewidth predict that treatment with carbogen gas combined with a perfluorocarbon emulsion will increase radiosensitivity more than either treatment alone, which agrees with the known effects of these treatments on hypoxic fraction. High-resolution maps show that tumor response to each treatment is spatially heterogeneous, and that there is a paradoxical response to the treatments in 7-12% of tumor pixels. Because HiSS MRI emphasizes changes in necrotic and/or hemorrhagic regions, it is more sensitive to oxygenation changes compared to conventional MRI. These results demonstrate that HiSS MRI is a practical, noninvasive method that could be used to choose the treatment that maximizes the size and extent of increases in tumor oxygenation for individual p...
High spectral and spatial resolution (HiSS) MR data were acquired at 1.5 T using echo-planar spec... more 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.
High spectral and spatial resolution (HiSS) data, acquired with echo-planar spectroscopic imaging... more High spectral and spatial resolution (HiSS) data, acquired with echo-planar spectroscopic imaging (EPSI), can be used to acquire water spectra from each small image voxel. These images are sensitive to changes in local susceptibility caused by superparamagnetic iron oxide particles (SPIO); therefore, we hypothesized that images derived from HiSS data are very sensitive to tumor neovasculature following injection of SPIO. Accurate image registration was used to validate HiSS detection of neovasculature with histology and micro-computed tomographic (microCT) angiography. Athymic nude mice and Copenhagen rats were inoculated with Dunning AT6.1 prostate tumor cells in the right hind limb. The tumor region was imaged pre- and post-intravenous injection of SPIO. Three-dimensional assemblies of the CD31-stained histologic slices of the mouse legs and the microCT images of the rat vascular casts were registered with EPSI. The average distance between HiSS-predicted regions of high vascular ...
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Papers by Marta Zamora