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Gregory S Karczmar

Publications and source records attributed to Gregory S Karczmar.

At least 19 recordsLinked to original sources
PubMed2006

Multi-slice DCE-MRI data using P760 distinguishes between metastatic and non-metastatic rodent prostate tumors.

An intermediate molecular weight contrast agent P760 was used to investigate the ability of multi-slice dynamic contrast-enhanced MRI (DCE-MRI) to distinguish metastatic from non-metastatic rodent prostate tumors. Non-metastatic AT2.1 and metastatic AT3.1 prostate tumors originally derived from the Dunning prostate cancer model were implanted on the hind leg of Copenhagen rats. Multi-sliced DCE-MRI data were acquired on a SIGNA 1.5 T scanner and analyzed using a recently developed empirical mathematical model. The P760 multi-slice DCE-MRI data in combination with the empirical mathematical model successfully distinguished between metastatic and non-metastatic rodent prostate tumors. Specifically, fitting the data with the empirical model showed that metastatic tumors had significantly faster contrast media uptake (p<0.001) and slower washout rates (p<0.01) than non-metastatic tumors.

Algorithms↗
PubMed2006

High spectral and spatial resolution MRI of breast lesions: preliminary clinical experience.

OBJECTIVE: 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. SUBJECTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Adult↗
PubMed2005

MRI of perfluorocarbon emulsion kinetics in rodent mammary tumours.

Perfluorocarbon (PFC) emulsions can be imaged directly by fluorine-19 MRI. We developed an optimized protocol for preparing PFC droplets of uniform size, evaluated use of the resulting droplets as blood pool contrast agents, studied their uptake by tumours and determined the spatial resolution with which they can be imaged at 4.7 T. Perfluorocarbon droplets of three different average sizes (324, 293 and 225 nm) were prepared using a microemulsifier. Images of PFC droplets with good signal-to-noise ratio were acquired with 625 microm in-plane resolution, 3 mm slice thickness and acquisition time of approximately 4.5 min per image. Kinetics of washout were determined using a simple mathematical model. The maximum uptake of the PFC droplets was three times greater at the tumour rim than in muscle, but the washout rate was two to three times slower in the tumour. The results are consistent with leakage of the droplets into the tumour extravascular space due to the hyper-permeability of tumour capillaries. PFC droplets may allow practical and quantitative measurements of blood volume and capillary permeability in tumours with reasonable spatial resolution.

Animals↗
PubMed2005

Anatomical and functional brain imaging using high-resolution echo-planar spectroscopic imaging at 1.5 Tesla.

High-resolution echo-planar spectroscopic imaging (EPSI) of water resonance (i.e. without water suppression) is proposed for anatomic and functional imaging of the human brain at 1.5 T. Water spectra with a resolution of 2.6 Hz and a bandwidth of 333 Hz were obtained in small voxels (1.7 x 1.7 x 3 mm3) across a single slice. Although water spectra appeared Lorentzian in most of the voxels in the brain, non-Lorentzian broadening of the water resonance was observed in voxels containing blood vessels. In functional experiments with a motor task, robust activation in motor cortices was observed in high-resolution T2* maps generated from the EPSI data. Shift of the water resonance frequency occurred during neuronal activation in motor cortices. The activation areas appeared to be more localized after excluding the voxels in which the lineshape of the water resonance had elevated T2* and became more non-Lorentzian during the motor task. These preliminary results suggest that high-resolution EPSI is a promising tool to study susceptibility-related effects, such as BOLD contrast, for improved anatomical and functional imaging of the brain.

Adult↗
PubMed2005

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.

Animals↗
PubMed2004

New model for analysis of dynamic contrast-enhanced MRI data distinguishes metastatic from nonmetastatic transplanted rodent prostate tumors.

Dynamic contrast-enhanced MRI (DCEMRI) data were acquired from metastatic and nonmetastatic tumors in rodents to follow the uptake and washout of a low-molecular-weight contrast agent (Gd-DTPA) and a contrast agent with higher molecular weight (P792). The concentration vs. time curves calculated for the tumor rims and centers were analyzed using the two-compartment model (TCM) and a newly developed empirical mathematical model (EMM). The EMM provided improved fits to the experimental data compared to the TCM. Parameters derived from the empirical model showed that the contrast agent washout rate was significantly slower in metastatic tumors than in nonmetastatic tumors for both Gd-DTPA (P < 0.03) and P792 (P < 0.04). The effects of the tumor on blood flow in "normal" tissue immediately adjacent to the tumors were evident: Gd-DTPA uptake and washout rates were much lower in muscle near the tumor (P < 0.05) than normal muscle farther from the tumor. The results suggest that accurate fits of DCEMRI data provide kinetic parameters that distinguish between metastatic and relatively benign cancers. In addition, a comparison of the dynamics of Gd-DTPA and P792 provides information regarding the microenvironment of tumors.

Animals↗
PubMed2004

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.

Body Water↗
PubMed2004

Estimating the arterial input function using two reference tissues in dynamic contrast-enhanced MRI studies: fundamental concepts and simulations.

In dynamic contrast-enhanced MRI (DCE-MRI) studies, an accurate knowledge of the arterial contrast agent concentration as a function of time is crucial for the estimation of kinetic parameters. In this work, a novel method for estimating the arterial input function (AIF) based on the contrast agent concentration-vs.-time curves in two different reference tissues is described. It is assumed that the AIFs of the two tissues have the same shape, and that simple models with two or more compartments, and unknown kinetic parameters, can describe their tracer concentration-vs.-time curves. Based on the principle of self-consistency, one can relate the two tracer concentration-vs.-time curves to estimate their common underlining AIF, together with the kinetic parameters of the two tissues. In practice, the measured concentration-vs.-time curves have noise, and the AIFs of the two tissues are not exactly the same due to different dispersion effects. These factors will produce errors in the AIF estimate. Simulation studies show that despite the two error sources, the double-reference-tissue method provides reliable estimates of the AIF.

Arteries↗
PubMed2003

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

PURPOSE: To evaluate the effect of varying spectral resolution on image quality of high spectral and spatial resolution (HiSS) images. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Breast↗
PubMed2003

Quantitative tumor oxymetric images from 4D electron paramagnetic resonance imaging (EPRI): methodology and comparison with blood oxygen level-dependent (BOLD) MRI.

This work presents a methodology for obtaining quantitative oxygen concentration images in the tumor-bearing legs of living C3H mice. The method uses high-resolution electron paramagnetic resonance imaging (EPRI). Enabling aspects of the methodology include the use of injectable, narrow, single-line triaryl methyl spin probes and an accurate model of overmodulated spectra. Both of these increase the signal-to-noise ratio (SNR), resulting in high resolution in space (1 mm)(3) and oxygen concentrations (approximately 3 torr). Thresholding at 15% the maximum spectral amplitude gives leg/tumor shapes that reproduce those in photographs. The EPRI appears to give reasonable oxygen partial pressures, showing hypoxia (approximately 0-6 torr, 0-10(3) Pa) in many of the tumor voxels. EPRI was able to detect statistically significant changes in oxygen concentrations in the tumor with administration of carbogen, although the changes were not increased uniformly. As a demonstration of the method, EPRI was compared with nearly concurrent (same anesthesia) T(2)*/blood oxygen level-dependent (BOLD) MRI. There was a good spatial correlation between EPRI and MRI. Homogeneous and heterogeneous T(2)*/BOLD MRI correlated well with the quantitative EPRI. This work demonstrates the potential for EPRI to display, at high spatial resolution, quantitative oxygen tension changes in the physiologic response to environmental changes.

Animals↗
PubMed2003

Reduction of spectral ghost artifacts in high-resolution echo-planar spectroscopic imaging of water and fat resonances.

Echo-planar spectroscopic imaging (EPSI) can be used for fast spectroscopic imaging of water and fat resonances at high resolution to improve structural and functional imaging. Because of the use of oscillating gradients during the free induction decay (FID), spectra obtained with EPSI are often degraded by Nyquist ghost artifacts arising from the inconsistency between the odd and even echoes. The presence of the spectral ghost lines causes errors in the evaluation of the true spectral lines, and this degrades images derived from high-resolution EPSI data. A technique is described for reducing the spectral ghost artifacts in EPSI of water and fat resonances, using echo shift and zero-order phase corrections. These corrections are applied during the data postprocessing. This technique is demonstrated with EPSI data acquired from human brains and breasts at 1.5 Tesla and from a water phantom at 4.7 Tesla. Experimental results indicate that the present approach significantly reduces the intensities of spectral ghosts. This technique is most useful in conjunction with high-resolution EPSI of water and fat resonances, but is less applicable to EPSI of metabolites due to the complexity of the spectra.

Adipose Tissue↗
PubMed2003

Using high spectral and spatial resolution bold MRI to choose the optimal oxygenating treatment for individual cancer patients.

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 patients.

Animals↗
PubMed2002

Effect of carbogen on tumor oxygenation: combined fluorine-19 and proton MRI measurements.

PURPOSE: Blood oxygen level dependent (BOLD) contrast in magnetic resonance imaging (MRI) has been widely used for noninvasive evaluation of the effects of tumor-oxygenating agents. However, there have been few tests of the validity of this method. The goal of the present work was to use the T(1) of fluorine-19 in perfluorocarbon (PFC) emulsions as a "gold standard" for comparison with BOLD MRI. MATHODS AND MATERIALS: Rats bearing R3230AC tumors implanted in the hind limb were injected with an emulsion of perfluoro-15-crown-5-ether for 2-3 days before experiments, which ensured that the PFC emulsion concentrated in the tumors. We correlated changes in tumor oxygenation caused by carbogen inhalation measured by (1)H BOLD MRI with quantitative (19)F measurements. The (19)F spin-lattice relaxation rate R(1) (= 1/T(1)) was measured to determine initial oxygen tension (pO(2)) in each image pixel containing the PFC, and changes in pO(2) during carbogen (95% O(2), 5% CO(2)) breathing. In a second carbogen breathing period, changes in water signal linewidth were measured using high spectral and spatial resolution imaging. (19)F and (1)H measurements were used to classify pixels as responders to carbogen (pixels where oxygen increased significantly) or nonresponders (no significant change in tumor oxygenation). RESULTS: The (19)F and (1)H measurements agreed in 65% +/- 11% of pixels (n = 14). Agreement was even stronger among pixels where (1)H showed increased oxygenation; (19)F measurements agreed with (1)H measurements in over 79% +/- 11% of these pixels. Similarly, there was strong agreement between the two modalities in pixels where (19)F reported no change in pO(2); (1)H also showed no changes in 76% +/- 18% of these pixels. Quantitative correlation of changes T(2)* (DeltaT(2)*) in (1)H and changes R(1) (DeltaR(1)) in (19)F was weak during carbogen breathing, and averaged over the whole tumor was approximately 0.40 for 14 experiments. However, the spatial patterns of (1)H and (19)F changes were qualitatively very similar. In hypoxic regions that were identified based on long (19)F T(1) (>2.53 s), (19)F and (1)H MRI agreed that carbogen had relatively weak effects. CONCLUSIONS: These results suggest that (1)H BOLD MRI reliably identifies increases in tumor pO(2). In hypoxic regions where increases in pO(2) are most desirable, carbogen was ineffective. The data suggest that (19)F and (1)H MRI can be used individually or in combination to guide the design of improved tumor-oxygenating agents.

Animals↗
PubMed2002

MRI of the tumor microenvironment.

The microenvironment within tumors is significantly different from that in normal tissues. A major difference is seen in the chaotic vasculature of tumors, which results in unbalanced blood supply and significant perfusion heterogeneities. As a consequence, many regions within tumors are transiently or chronically hypoxic. This exacerbates tumor cells' natural tendency to overproduce acids, resulting in very acidic pH values. The hypoxia and acidity of tumors have important consequences for antitumor therapy and can contribute to the progression of tumors to a more aggressive metastatic phenotype. Over the past decade, techniques have emerged that allow the interrogation of the tumor microenvironment with high resolution and molecularly specific probes. Techniques are available to interrogate perfusion, vascular distribution, pH, and pO(2) nondestructively in living tissues with relatively high precision. Studies employing these methods have provided new insights into the causes and consequences of the hostile tumor microenvironment. Furthermore, it is quite exciting that there are emerging techniques that generate tumor image contrast via ill-defined mechanisms. Elucidation of these mechanisms will yield further insights into the tumor microenvironment. This review attempts to identify techniques and their application to tumor biology, with an emphasis on nuclear magnetic resonance (NMR) approaches. Examples are also discussed using electron MR, optical, and radionuclear imaging techniques.

Animals↗
PubMed2002

Imaging spin probe distribution in the tumor of a living mouse with 250 MHz EPR: correlation with BOLD MRI.

Electron paramagnetic resonance imaging (EPRI) promises to provide new insights into the physiology of tissues in health and disease. Understanding the in vivo imaging capability of this new modality requires comparison with other physiologically responsive techniques. Here, an initial comparison between 2D EPR spatial imaging of a narrow single line injectable paramagnetic trityl spin probe and 2D slice-selected carbogen subtraction BOLD MRI is presented. The images were obtained from the same FSa fibrosarcoma grown in the leg of a C3H mouse. This tumor was unusual in comparison with others imaged with subtraction BOLD MRI because of its peripheral distribution of intensity. The spatial distribution of the EPR spin probe showed the same peripheral distribution. The pixel resolutions of these images are comparable. These images provide an early in vivo comparison of EPRI with a well-established imaging modality. The comparison validates the in vivo distribution of spin probe as imaged with EPRI, and provides a proof of principle for the comparison of BOLD and EPRI.

Animals↗
PubMed2002

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.

Adenocarcinoma↗
PubMed2002

Effects of constant frequency noise in magnetic resonance imaging with nonuniform k-space sampling.

Magnetic resonance images can be compromised by constant frequency (CF) noise, such as radio frequency (RF) noise. We investigate the effects of CF noise in four imaging methods with non-uniform k-space sampling: single-shot echo-planar imaging (EPI) with sinusoidal readout gradients, phase-encoded echo-planar spectroscopic imaging (EPSI) with sinusoidal readout gradients, projection-reconstruction imaging, and single-shot spiral imaging. The characteristics of the CF artifacts in each imaging method are studied with numerical simulations. CF noise is found to cause artifacts of nonclassic forms in the reconstructed images. Specifically, dashed-line, streak, and spiral patterns of CF noise appear in EPI/EPSI with sinusoidal readout gradients, projection-reconstruction imaging, and spiral imaging, respectively. The analytical expression for dashed-line artifacts is found to be a weighted sum of Bessel functions and is verified with in vivo experiments. The CF artifacts can be removed during post-processing by eliminating the noise spikes in the Fourier domain of the raw data.

Animals↗