Gregory S Karczmar

University of Chicago, Chicago, Illinois, United States

Are you Gregory S Karczmar?

Claim your profile

Publications (132)321.61 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: To compare DCE-MRI parameters from scans of breast lesions at 1.5 Tesla and 3 Tesla. Eleven patients underwent paired MRI examinations on both Philips 1.5T and 3T systems using a standard clinical fat-suppressed, T1-weighted DCE-MRI protocol, with 70-76 s temporal resolution. Signal intensity-versus-time curves were fit with an empirical mathematical model to obtain semi-quantitative measures of uptake and washout rates as well as time-to-peak enhancement (TTP). Maximum percent enhancement and signal enhancement ratio (SER) were also measured for each lesion. Percent differences between parameters measured at the two field strengths were compared. TTP and SER parameters measured at 1.5T and 3T were similar; with mean absolute differences of 19% and 22% respectively. Maximum percent signal enhancement was significantly higher at 3T than at 1.5T (p=0.006). Qualitative assessment showed that image quality was significantly higher at 3T (p=0.005). Our results suggest that TTP and SER are more robust to field strength change than other measured kinetic parameters and therefore measurements of these parameters can be more easily standardized than measurements of other parameters derived from DCE-MRI. Semi-quantitative measures of overall kinetic curve shape showed higher reproducibility than discrete classification of kinetic curve early and delayed phases in a majority of the cases studied. Advances in knowledge: Qualitative measures of curve shape are not consistent across field strength even when acquisition parameters are standardized. Quantitative measures of overall kinetic curve shape, in contrast, have higher reproducibility.
    The British journal of radiology 03/2015; DOI:10.1259/bjr.20150021 · 2.11 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Widely used MRI methods show brain morphology both in vivo and ex vivo at very high resolution. Many of these methods (e.g., T2 (*)-weighted imaging, phase-sensitive imaging, or susceptibility-weighted imaging) are sensitive to local magnetic susceptibility gradients produced by subtle variations in tissue composition. However, the spectral resolution of commonly used methods is limited to maintain reasonable run-time combined with very high spatial resolution. Here, the authors report on data acquisition at increased spectral resolution, with 3-dimensional high spectral and spatial resolution MRI, in order to analyze subtle variations in water proton resonance frequency and lineshape that reflect local anatomy. The resulting information compliments previous studies based on T2 (*) and resonance frequency. The proton free induction decay was sampled at high resolution and Fourier transformed to produce a high-resolution water spectrum for each image voxel in a 3D volume. Data were acquired using a multigradient echo pulse sequence (i.e., echo-planar spectroscopic imaging) with a spatial resolution of 50 × 50 × 70 μm(3) and spectral resolution of 3.5 Hz. Data were analyzed in the spectral domain, and images were produced from the various Fourier components of the water resonance. This allowed precise measurement of local variations in water resonance frequency and lineshape, at the expense of significantly increased run time (16-24 h). High contrast T2 (*)-weighted images were produced from the peak of the water resonance (peak height image), revealing a high degree of anatomical detail, specifically in the hippocampus and cerebellum. In images produced from Fourier components of the water resonance at -7.0 Hz from the peak, the contrast between deep white matter tracts and the surrounding tissue is the reverse of the contrast in water peak height images. This indicates the presence of a shoulder in the water resonance that is not present at +7.0 Hz and may be specific to white matter anatomy. Moreover, a frequency shift of 6.76 ± 0.55 Hz was measured between the molecular and granular layers of the cerebellum. This shift is demonstrated in corresponding spectra; water peaks from voxels in the molecular and granular layers are consistently 2 bins apart (7.0 Hz, as dictated by the spectral resolution) from one another. High spectral and spatial resolution MR imaging has the potential to accurately measure the changes in the water resonance in small voxels. This information can guide optimization and interpretation of more commonly used, more rapid imaging methods that depend on image contrast produced by local susceptibility gradients. In addition, with improved sampling methods, high spectral and spatial resolution data could be acquired in reasonable run times, and used for in vivo scans to increase sensitivity to variations in local susceptibility.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: IntroductionPrevious work from this laboratory demonstrated that magnetic resonance imaging (MRI) detects early murine mammary cancers and reliably differentiates between in situ and invasive cancer. Based on this previous work, we used MRI to study initiation and progression of murine mammary cancer, and monitor the transition from the in situ to the invasive phase.Methods In total, seven female C3(1) SV40 Tag mice were imaged every two weeks between the ages of 8 to 23 weeks. Lesions were identified on T2-weighted images acquired at 9.4 Tesla based on their morphology and growth rates. Lesions were traced manually on MR images of each slice. Volume of each lesion was calculated by adding measurements from individual slices. Plots of lesion volume versus time were analyzed to obtain the specific growth rate (SGR). The time at which in situ cancers (referred to as `mammary intraepithelial neoplasia (MIN)¿) and invasive cancers were first detected; and the time at which in situ cancers became invasive were recorded.ResultsA total of 121 cancers (14 to 25 per mouse) were identified in seven mice. On average the MIN lesions and invasive cancers were first detected when mice were 13 and 18 weeks old, respectively. The average SGR was 0.47¿±¿0.18 week-1 and there were no differences (P >0.05) between mice. 74 lesions had significantly different tumor growth rates before and after ~17 weeks of age; with average doubling times (DT) of 1.88 and 1.27 weeks, respectively. The average DT was significantly shorter (P <0.0001) after 17 weeks of age. However, the DT for some cancers was longer after 17 weeks of age, and about 10% of the cancers detected did not progress to the invasive stage.ConclusionsA wide range of growth rates were observed in SV40 mammary cancers. Most cancers transitioned to a more aggressive phenotype at approximately 17 weeks of age, but some cancers became less aggressive. The results suggest that the biology of mammary cancers is extremely heterogeneous. This work is a first step towards use of MRI to improve understanding of factors that control and/or signal the development of aggressive breast cancer.
    Breast cancer research: BCR 12/2014; 16(6):495. DOI:10.1186/s13058-014-0495-6 · 5.88 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: This pilot study compared the detectability of internal thermal marks produced with MRI-guided focused ultrasound (MRgFUS) on MRI, computed tomography (CT), ultrasonography (US), and color images from digital scanning. Internal marks made using MRgFUS could potentially guide surgical, biopsy or radiotherapy procedures. New Zealand White rabbits (n = 6) thigh muscle were marked using a Philips MRgFUS system. Before and after sonications, rabbits were imaged using T1- and T2-weighted MRI. Then rabbits were sacrificed and imaging was performed using CT and US. After surgical excision specimens were scanned for color conspicuity analysis. Images were read by a radiologist and quantitative analysis of signal intensity was calculated for marks and normal muscle. Of a total of 19 excised marks, approximately 79%, 63%, and 62% were visible on MRI, CT, and US, respectively. The average maximum temperature elevation in the marks during MRgFUS was 39.7 ± 10.1 °C, and average dose diameter (i.e., the diameter of the area that achieved a thermal dose greater than 240 cumulative equivalent minutes at 43 °C) of the mark at the focal plane was 7.3 ± 2.1 mm. On MRI the average normalized signal intensities were significantly higher in marks compared to normal muscle (p < 0.05). On CT, the marked regions were approximately 10 HU lower than normal muscle (p < 0.05). The results demonstrate that MRgFUS can be used to create internal marks that are visible on MRI, CT and US.
    Physica Medica 12/2014; DOI:10.1016/j.ejmp.2014.04.007 · 1.85 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: We previously showed that epidermal growth factor receptor (EGFR) promotes tumorigenesis in the azoxymethane/dextran sulfate sodium (AOM/DSS) model, whereas vitamin D (VD) suppresses tumorigenesis. EGFR-vitamin D receptor (VDR) interactions, however, are incompletely understood. VD inhibits the renin-angiotensin system (RAS), whereas RAS can activate EGFR. We aimed to elucidate EGFR-VDR cross-talk in colorectal carcinogenesis. Experimental Design: To examine VDR-RAS interactions, we treated Vdr+/+ and Vdr-/- mice with AOM/DSS. Effects of VDR on RAS and EGFR were examined by Westerns, immunostaining and real time PCR. We also examined the effect of vitamin D3 on colonic RAS in Vdr+/+ mice. EGFR regulation of VDR was examined in hypomorphic Egfr ((Wa2)) and Egfr(wildtype) mice. Ang II-induced EGFR activation was studied in cell culture. Results: Vdr deletion significantly increased tumorigenesis, activated EGFR and β catenin signaling and increased colonic RAS components: including renin and angiotensin II. Dietary VD3 supplementation suppressed colonic renin. Renin was increased in human colon cancers. In studies in vitro, Ang II activated EGFR and stimulated colon cancer cell proliferation by an EGFR-mediated mechanism. Ang II also activated macrophages and colonic fibroblasts. Compared to tumors from Egfr(Waved2) mice, tumors from Egfr(wildtype) mice showed up-regulated Snail1, a suppressor of VDR, and down-regulated VDR. Conclusions: VDR suppresses the colonic RAS cascade, limits EGFR signals and inhibits colitis-associated tumorigenesis, whereas EGFR increases Snail1 and down-regulates VDR in colonic tumors. Taken together, these results uncover a RAS-dependent mechanism mediating EGFR and VDR cross-talk in colon cancer.
    Clinical Cancer Research 09/2014; DOI:10.1158/1078-0432.CCR-14-0209 · 8.19 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The purpose of this study was to use high resolution 3D MRI to study mouse mammary gland ductal architecture based on intra-ductal injection of contrast agents. Female FVB/N mice age 12–20 weeks (n = 12), were used in this study. A 34G, 45° tip Hamilton needle with a 25uL Hamilton syringe was inserted into the tip of the nipple. Approximately 20–25uL of a Gadodiamide/Trypan blue/saline solution was injected slowly over one minute into the nipple and duct. To prevent washout of contrast media from ducts due to perfusion, and maximize the conspicuity of ducts on MRI, mice were sacrificed one minute after injection. High resolution 3D T1-weighted images were acquired on a 9.4 T Bruker scanner after sacrifice to eliminate motion artifacts and reduce contrast media leakage from ducts. Trypan blue staining was well distributed throughout the ductal tree. MRI showed the mammary gland ductal structure clearly. In spoiled gradient echo T1-weighted images, the signal-to-noise ratio of regions identified as enhancing mammary ducts following contrast injection was significantly higher than that of muscle (p < 0.02) and significantly higher than that of contralateral mammary ducts that were not injected with contrast media (p < 0.0001). The methods described here could be adapted for injection of specialized contrast agents to measure metabolism or target receptors in normal ducts and ducts with in situ cancers.
    Magnetic Resonance Imaging 08/2014; DOI:10.1016/j.mri.2014.08.035 · 2.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: OBJECTIVE. The purpose of this study was to evaluate the effect of increasing the spatial resolution of the prostate DWI protocol on image quality and lesion conspicuity. SUBJECTS AND METHODS. Twenty-nine patients with biopsy-proven prostate cancer undergoing MRI examinations were imaged with two diffusion-weighted imaging (DWI) protocols: current standard clinical protocol (6.7 mm(3) voxels) and a new high-resolution protocol (3.1 mm(3) voxels). Diffusion-weighted images were independently and subjectively scored on lesion conspicuity, internal architecture definition, and overall image quality by two radiologists. Average apparent diffusion coefficient (ADC) values were measured in normal tissue and cancerous lesions on both sequences. Reader scores and ADC and contrast values were compared between the two protocols. Cancer ADC values were correlated with Gleason scores. RESULTS. The signal-to-noise ratio of the new high-resolution DWI protocol was 40% lower than that of the standard protocol. The reader scores were higher by 0.73 (range, 0.29-1.16) grades, or 19% (range, 7-32%), on average, for the new protocol, indicating better image quality. The average ADC values were 8% higher with the new protocol, with ADC contrast values between cancer and normal prostate unchanged. There was marginally significant correlation of cancer ADC values with Gleason scores (p = 0.05, r ≈ -0.36). CONCLUSION. We showed that for DWI of the prostate at 3-7 mm(3) voxel sizes the benefits of higher spatial resolution outweigh the effects of reduced signal-to-noise and contrast-to-noise ratios, potentially improving the sensitivity to small or sparse prostate cancers. Radiologists can consider using higher-spatial-resolution DWI sequences in their practices.
    American Journal of Roentgenology 07/2014; 203(1):85-90. DOI:10.2214/AJR.13.11098 · 2.74 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Evaluate qualitative dynamic contrast-enhanced magnetic resonance imaging (MRI) characteristics of normal central zone based on recently described central zone MRI features. Institutional review board-approved, Health Insurance Portability and Accountability Act compliant study, 59 patients with prostate cancer, histopathology proven to not involve central zone or prostate base, underwent endorectal MRI before prostatectomy. Two readers independently reviewed T2-weighted images and apparent diffusion coefficient (ADC) maps identifying normal central zone based on low signal intensity and location. Next, two readers drew bilateral central zone regions of interest on dynamic contrast-enhanced magnetic resonance images in consensus and independently recorded enhancement curve types as type 1 (progressive), type 2 (plateau), and type 3 (wash-out). Identification rates of normal central zone and enhancement curve type were recorded and compared for each reviewer. The institutional review board waiver was approved and granted 05/2010. Central zone identified in 92%-93% of patients on T2-weighted images and 78%-88% on ADC maps without significant difference between identification rates (P = .63 and P = .15 and inter-reader agreement (κ) is 0.64 and 0.29, for T2-weighted images and ADC maps, respectively). All central zones were rated either curve type 1 or curve type 2 by both radiologists. No statistically significant difference between the two radiologists (P = .19) and inter-reader agreement was κ = 0.37. Normal central zone demonstrates either type 1 (progressive) or type 2 (plateau) enhancement curves on dynamic contrast-enhanced MRI that can be potentially useful to differentiate central zone from prostate cancer that classically demonstrates a type 3 (wash-out) enhancement curve.
    Academic radiology 05/2014; 21(5):569-77. DOI:10.1016/j.acra.2014.01.013 · 2.09 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: High spectral and spatial resolution magnetic resonance imaging (HiSS MRI) yields information on the local environment of suspicious lesions. Previous work has demonstrated the advantages of HiSS (complete fat-suppression, improved image contrast, no required contrast agent, etc.), leading to initial investigations of water resonance lineshape for the purpose of breast lesion classification. The purpose of this study is to investigate a quantitative imaging biomarker, which characterizes non-Lorentzian components of the water resonance in HiSS MRI datasets, for computer-aided diagnosis (CADx).Methods: The inhomogeneous broadening and non-Lorentzian or "off-peak" components seen in the water resonance of proton spectra of breast HiSS images are analyzed by subtracting a Lorentzian fit from the water peak spectra and evaluating the difference spectrum or "residual." The maxima of these residuals (referred to hereafter as "off-peak components") tend to be larger in magnitude in malignant lesions, indicating increased broadening in malignant lesions. The authors considered only those voxels with the highest magnitude off-peak components in each lesion, with the number of selected voxels dependent on lesion size. Our voxel-based method compared the magnitudes and frequencies of off-peak components of all voxels from all lesions in a database that included 15 malignant and 8 benign lesions (yielding ∼3900 voxels) based on the lesions' biopsy-confirmed diagnosis. Lesion classification was accomplished by comparing the average off-peak component magnitudes and frequencies in malignant and benign lesions. The area under the ROC curve (AUC) was used as a figure of merit for both the voxel-based and lesion-based methods.Results: In the voxel-based task of distinguishing voxels from malignant and benign lesions, off-peak magnitude yielded an AUC of 0.88 (95% confidence interval [0.84, 0.91]). In the lesion-based task of distinguishing malignant and benign lesions, average off-peak magnitude yielded an AUC 0.83 (95% confidence interval [0.61, 0.98]).Conclusions: These promising AUC values suggest that analysis of the water-resonance in each HiSS image voxel using "residual analysis" could have high diagnostic utility and could be used to enhance current CADx methods and allow detection of breast cancer without the need to inject contrast agents.
    Medical Physics 01/2014; 41(1):012303. DOI:10.1118/1.4851615 · 3.01 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Neonatal necrotizing enterocolitis (NEC) is a poorly understood life-threatening illness afflicting premature infants. Research is hampered by the absence of a suitable method to monitor disease progression noninvasively. The primary goal of this research was to test in vivo MRI methods for the noninvasive early detection and staging of inflammation in the ileum of an infant rat model of NEC. Neonatal rats were delivered by cesarean section at embryonic stage of day 20 after the beginning of pregnancy and stressed with formula feeding, hypoxia and bacterial colonization to induce NEC. Naturally born and dam-fed neonatal rats were used as healthy controls. In vivo MRI studies were performed using a Bruker 9.4-T scanner to obtain high-resolution anatomical MR images using both gradient echo and spin echo sequences, pixel-by-pixel T2 maps using a multi-slice-multi-echo sequence, and maps of the apparent diffusion coefficient (ADC) of water using a spin echo sequence, to assess the degree of ileal damage. Pups were sacrificed at the end of the MRI experiment on day 2 or 4 for histology. T2 measured by MRI was increased significantly in the ileal regions of pups with NEC by histology (106.3 ± 6.1 ms) compared with experimentally stressed pups without NEC (85.2 ± 6.8 ms) and nonstressed, control rat pups (64.9 ± 2.3 ms). ADC values measured by diffusion-weighted MRI were also increased in the ileal regions of pups with NEC by histology [(1.98 ± 0.15) × 10(-3) mm(2) /s] compared with experimentally stressed pups without NEC [(1.43 ± 0.16) × 10(-3) mm(2) /s] and nonstressed control pups [(1.10 ± 0.06) × 10(-3) mm(2) /s]. Both T2 and ADC values between these groups were found to be significantly different (p < 0.03). The correlation of MRI results with histologic images of the excised ileal tissue samples strongly suggests that MRI can noninvasively identify NEC and assess intestinal injury prior to clinical symptoms in a physiologic rat pup model of NEC. © 2013 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd.
    NMR in Biomedicine 12/2013; DOI:10.1002/nbm.3060 · 3.56 Impact Factor
  • Gregory Stanislaus Karczmar
    [Show abstract] [Hide abstract]
    ABSTRACT: LEARNING OBJECTIVES 1) Gain familiarity with methods used for accurate measurements of tumor volumes with MRI, advantages of MRI, challenges, and sources of error. 2) Understand basic principles and clinical applications of dynamic contrast enhanced MRI; possibilities for standardized measurements of perfusion and capillary permeability, and sources of error. 3) Understand basic principles and clinical applications of diffusion-weighted imaging, measurements of the ‘apparent coefficient of diffusion’ (ADC), and sources of error. ABSTRACT Anatomic and functional MRI is increasingly used for diagnosis and staging of cancer, and for detection of response to therapy. However, standardized, quantitative measurements remain challenging. We will review use of MRI to reliably measure tumor volume, and two widely used functional MRI methods – dynamic contrast enhanced MRI (DCEMRI) and diffusion-weighted imaging (DWI). We will discuss methods used to standardize DCEMRI measurements, including quantitative measurements of contrast media as a function of time, measurement of the arterial input function, and use of an appropriate model for calculation of perfusion/capillary permeability, as well as 'model-free' approaches. We will discuss methods used to measure the apparent diffusion constant (ADC) and the relationship between the ADC and underlying physiology/anatomy at the microscopic level.
    Radiological Society of North America 2013 Scientific Assembly and Annual Meeting; 12/2013
  • William Weiss, Milica Medved, Gregory Stanislaus Karczmar, Maryellen L. Giger
    [Show abstract] [Hide abstract]
    ABSTRACT: PURPOSE Water resonance lineshape characteristics – acquired using high spectral and spatial resolution (HiSS) MRI – have been shown to discriminate between benign and malignant breast lesions. Here, we present a novel approach to the analysis of water resonance lineshape by comparing dispersion vs. absorption components (DISPA) plots of spectra obtained from HiSS datasets to those of an ideal Lorentzian lineshape, in an attempt to characterize overall spectral shape differences between malignant and benign breast lesions. METHOD AND MATERIALS HiSS MR images were collected under an IRB-approved protocol. Following image and spectral reconstruction, water resonance spectra are obtained in each small voxel and normalized to their peak amplitude. A phase correction is applied by maximizing the integral of the real part of each complex water resonance. A 2D DISPA plot is created by plotting the real vs. the imaginary spectrum. These plots are compared to that of a perfectly phased Lorentzian peak - a circle with diameter 1, intersecting the origin and symmetric about the x-axis. The difference between the DISPA plots and the ideal Lorentzian is defined as the square-root of the sum of squared distances from each spectral point to the Lorentzian circle. This difference metric is calculated for every voxel in each lesion. We examine the voxels exhibiting the top 10% of differences in each lesion, but including no less than 10 and no more than 50 voxels. Using ROC analysis, the DISPA differences in each voxel, as well as the mean and variance of those in each lesion, were evaluated using the clinical biopsied diagnosis (15 malignant; 8 benign lesions) as truth, and the performances of these features were assessed using the area under the ROC curve (AUC) as the figure of merit. RESULTS In the task of distinguishing between malignant and benign lesions, ROC analysis of DISPA differences on all voxels, as well as on their mean and variance over entire lesions, yielded AUC values of 0.82±0.02, 0.77±0.09, and 0.86±0.08, respectively. CONCLUSION We present a new spectral-analysis technique to quantify distortions in the shape of the water resonance of voxels in breast lesions, yielding a predictor of malignancy. CLINICAL RELEVANCE/APPLICATION A novel HiSS MRI spectral-analysis approach reveals more general spectral distortions than Fourier component analysis and may improve the performance of CADx systems when classifying breast lesions.
    Absorption (DISPA) Plots to Quantify Water Resonance Distortions. Radiological Society of North America 2013 Scientific Assembly and Annual Meeting; 12/2013
  • [Show abstract] [Hide abstract]
    ABSTRACT: PURPOSE To evaluate the short term reproducibility of DW-MR imaging of the prostate through consistency in ADC maps between subsequent scans of the same patient using the same scanner and identical imaging parameters. METHOD AND MATERIALS 14 patients with biopsy proven prostate cancer were evaluated under an IRB-approved protocol. Each patient underwent two, identical DW-MRI scans gathered back-to-back with the patient remaining on the table between acquisitions. ADC maps for each scan were generated using a least squares fit and a deformable registration was performed on the scan pairs using the Plastimatch software employing a Demons algorithm. The prostate and ROIs within cancer lesions were delineated on each scan per patient by two radiologists using the b-0 images. The prostate volume was divided into sextants (anterior apex, posterior apex, anterior medial, posterior medial, anterior base, posterior base) and absolute and magnitude percentage difference in ADC per voxel was calculated and compared across sextants. Voxel-based as well as ROI-based variation in ADC was also calculated for cancerous ROIs. RESULTS The absolute difference in ADC per voxel within the prostate ranged from 2.33x10-10 to 1.60x10-3 mm2/sec (per voxel magnitude percentage difference of 0.00%-200%, mean 10.52%). Variation in ADC was found to be largest in the posterior apex (0.00%-200%, mean 11.55%) although difference between sextants was not statistically significant. Cancer ROIs showed a voxel-based difference in ADC per voxel of 1.07x10-6 to 8.41x10-4 mm2/sec (0.00%-67.37%, mean 11.16%). ROI-based analysis showed that the difference in mean ADC of a cancerous ROI between the two scans ranged from -4.22 x 10-4 to 4.63 x 10-4 mm2/sec with mean absolute difference 3.63 x 10-5 mm2/sec. CONCLUSION DW-MRI has strong potential to become a powerful quantitative imaging biomarker for prostate cancer but it is necessary to characterize the reproducibility of DW-MRI when using it in the clinic or developing new approaches for its use. Our data demonstrates that ADC variation within the prostate is modest, on the order of 10%. CLINICAL RELEVANCE/APPLICATION DW-MRI is a mainstay of MRI of prostate cancer, but although a fundamental limitation of its use in the clinic or as a potential quantitative biomarker, reproducibility has not been well established.
    Radiological Society of North America 2013 Scientific Assembly and Annual Meeting; 12/2013
  • [Show abstract] [Hide abstract]
    ABSTRACT: PURPOSE Colon cancer is a leading cause of cancer-deaths in the US. Ulcerative colitis is causally linked to colitis-associated neoplastic progression but is difficult to detect and monitor non-invasively. Goals of this study were to determine MRI characteristics of early colitis-associated colon cancer and to assess vitamin D chemopreventive efficacy. METHOD AND MATERIALS This study included CF1 female control mice (n=12), and mice treated with azoxymethane i.p. and dextran sulfate sodium in the drinking water (n=25) to induce colitis and colon cancer. Mice were fed a Western diet or Western diet supplemented with vitamin D (500 µg/kg chow). Western diets are relatively deficient in vitamin D and calcium. Mice were studied serially using anatomic and dynamic contrast enhanced MRI (DCEMRI) with a Gd-based contrast agent. In vivo MR and ex vivo histological images were co-registered using an agar based color-coded phantom in a flexible tube (2 mm o. d.) that was inserted via the rectum to the cecum. The phantom provided visual and MRI-detectable reference markers to co-register in vivo and ex vivo images. RESULTS We demonstrated that: 1) a visible reference marker could be used to successfully co-register MRI abnormalities with histological features identified in H&E stained sections; 2) T2 values distinguished normal colon from colitis, and from focal neoplastic lesions (p<0.005); 3) Ktrans values assessed by DCEMRI (a measure of perfusion/capillary permeability) reliably distinguished normal colon from tumor (0.12±0.01 min-1 vs. 0.61±0.05 min-1, respectively, p<0.001); 4) blood vessel diameters were >3-fold larger adjacent to early colonic tumors compared to vessels in control mice, suggesting that MRI might be used to detect dilated blood vessels as biomarkers of early colorectal cancer; 5) Vitamin D reduced the number of colonic tumors and degree of inflammation detected by MRI (p<0.001). CONCLUSION A novel technique was successfully developed to co-register MR and histological images. Several reliable image-based markers for colitis and colon cancer were identified. These MRI methods could monitor the chemopreventive efficacy of vitamin D in this model in real time and without sacrifice. CLINICAL RELEVANCE/APPLICATION Non-invasive MRI/DCEMRI studies of colitis and colon cancer in mice will improve understanding of these diseases, produce new MRI markers to improve diagnosis, and guide development of new therapies.
    Radiological Society of North America 2013 Scientific Assembly and Annual Meeting; 12/2013
  • [Show abstract] [Hide abstract]
    ABSTRACT: OBJECTIVE. The purpose of this article is to study relationships between MRI-based prostate volume and volume-adjusted serum prostate-specific antigen (PSA) concentration estimates and prostate cancer Gleason score. MATERIALS AND METHODS. The study included 61 patients with prostate cancer (average age, 63.3 years; range 52-75 years) who underwent MRI before prostatectomy. A semiautomated and MRI-based technique was used to estimate total and central gland prostate volumes, central gland volume fraction (central gland volume divided by total prostate volume), PSA density (PSAD; PSA divided by total prostate volume), and PSAD for the central gland (PSA divided by central gland volume). These MRI-based volume and volume-adjusted PSA estimates were compared with prostatectomy specimen weight and Gleason score by using Pearson (r) or Spearman (ρ) correlation coefficients. RESULTS. The estimated total prostate volume showed a high correlation with reference standard volume (r = 0.94). Of the 61 patients, eight (13.1%) had a Gleason score of 6, 40 (65.6%) had a Gleason score of 7, seven (11.5%) had a Gleason score of 8, and six (9.8%) had a Gleason score of 9 for prostate cancer. The Gleason score was significantly correlated with central gland volume fraction (ρ = -0.42; p = 0.0007), PSAD (ρ = 0.46; p = 0.0002), and PSAD for the central gland (ρ = 0.55; p = 0.00001). CONCLUSION. Central gland volume fraction, PSAD, and PSAD for the central gland estimated from MRI examinations show a modest but significant correlation with Gleason score and have the potential to contribute to personalized risk assessment for significant prostate cancer.
    American Journal of Roentgenology 11/2013; 201(5):1041-8. DOI:10.2214/AJR.13.10591 · 2.74 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To study the dependence of apparent diffusion coefficient (ADC) and T2 on echo time (TE) and b-value, respectively, in normal prostate and prostate cancer, using two-dimensional MRI sampling, referred to as "hybrid multidimensional imaging." The study included 10 patients with biopsy-proven prostate cancer who underwent 3 Tesla prostate MRI. Diffusion-weighted MRI (DWI) data were acquired at b = 0, 750, and 1500 s/mm(2) . For each b-value, data were acquired at TEs of 47, 75, and 100 ms. ADC and T2 were measured as a function of b-value and TE, respectively, in 15 cancer and 10 normal regions of interest (ROIs). The Friedman test was used to test the significance of changes in ADC as a function of TE and of T2 as a function of b-value. In normal prostate ROIs, the ADC at TE of 47 ms is significantly smaller than ADC at TE of 100 ms (P = 0.0003) and T2 at b-value of 0 s/mm(2) is significantly longer than T2 at b-value of 1500 s/mm(2) (P = 0.001). In cancer ROIs, average ADC and T2 values do not change as a function of TE and b-value, respectively. However, in many cancer pixels, there are large decreases in the ADC as a function of TE and large increases in T2 as a function of b-value. Cancers are more conspicuous in ADC maps at longer TEs. Parameters derived from hybrid imaging that depend on coupled/associated values of ADC and T2 may improve the accuracy of MRI in diagnosing prostate cancer. J. Magn. Reson. Imaging 2013. © 2013 Wiley Periodicals, Inc.
    Journal of Magnetic Resonance Imaging 08/2013; DOI:10.1002/jmri.24212 · 2.57 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose:To evaluate the feasibility and safety of magnetic resonance (MR) imaging-guided laser-based thermotherapy in men with clinically low-risk prostate cancer and a concordant lesion at biopsy and MR imaging.Materials and Methods:This HIPAA-compliant phase I prospective study was approved by the institutional review board. Informed consent was obtained from all patients. Transperineal MR imaging-guided focal laser ablation for clinically low-risk prostate cancer was performed in patients with a Gleason score of 7 or less in three or fewer cores limited to one sextant obtained with transrectal ultrasonography (US)-guided biopsy and a concordant lesion at MR imaging. Lesions were targeted with a laser ablation system. Periprocedural complications were recorded. The International Prostate Symptom Score (IPSS) and the Sexual Health Inventory for Men (SHIM) score were collected before and after the procedure. MR imaging-guided biopsy of the ablation zone was performed 6 months after treatment. The prostate-specific antigen level, IPSS, and SHIM score before and after ablation were compared by using the Wilcoxon signed rank test.Results:Treatment was successfully completed in nine patients (procedure duration, 2.5-4 hours; mean laser ablation duration, 4.3 minutes). Immediate contrast-enhanced posttreatment MR imaging showed a hypovascular defect in eight patients. Self-resolving perineal abrasion and focal paresthesia of the glans penis each occurred in one patient. The mean (±standard deviation) IPSS and SHIM score at baseline were 5.8 ± 5.3 and 19.0 ± 8.0, respectively. Average score changes were not significantly different from zero during follow-up (P = .18-.99). MR imaging-guided biopsy of the ablation zone showed no cancer in seven patients (78%) and Gleason grade 6 cancer in two (22%).Conclusion:Transperineal MR imaging-guided focal laser ablation appears to be a feasible and safe focal therapy option for clinically low-risk prostate cancer.© RSNA, 2013Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13121652/-/DC1.
    Radiology 02/2013; DOI:10.1148/radiol.13121652 · 6.21 Impact Factor
  • Gregory Stanislaus Karczmar
    [Show abstract] [Hide abstract]
    ABSTRACT: LEARNING OBJECTIVES 1) New approaches to magnetic resonance imaging and magnetic resonance spectroscopy of the breast. 2) Provide a brief overview of the technical aspects of each technique, and a review of the current evidence for the diagnostic utility of each approach. 3) Approaches to data acquisition and quantitative analysis in dynamic contrast enhanced MR Imaging; relative merits of High-temporal Resolution versus High-spatial Resolution. 4) New approaches to diffusion-weighted MR Imaging and promising applications of DCEMRI. 5) High-Resolution MR Imaging; what is the current resolution limit? 6) MR Imaging spectroscopy and approaches to combining ideas from imaging and spectroscopy. 7) Discuss promising markers for cancer that can be detected by spectroscopy. 8) Advantages of quantitative imaging. ABSTRACT Normal 0 false false false MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin- I will briefly explain the physical basis for selected approaches to breast MR imaging, how the images/data are acquired, the clinically relevant parameters that are measured, and the potential applications to improve diagnosis or to guide therapy. Specifically I will focus on: 1. Dynamic contrast enhanced MRI: Diffusion-weighted imaging provides information regarding tumor perfusion, capillary permeability, and cell density. I will discuss new quantitative approaches to acquisition and analysis of DCEMRI data, typical spatial and temporal resolution. I will discuss the advantages of high spatial resolution imaging (to study morphology) vs. high temporal resolution imaging (to study physiology) 2. Diffusion-weighted imaging: Diffusion weighted imaging is sensitive to cell density and micro-anatomy. I will review current approaches to data acquisition and clinical applications. 3. MR spectroscopy: I will discuss proton MR spectroscopy and high resolution spectroscopic imaging of water and fat.
    Radiological Society of North America 2012 Scientific Assembly and Annual Meeting; 11/2012
  • William Weiss, Milica Medved, Gregory Stanislaus Karczmar, Maryellen L. Giger
    [Show abstract] [Hide abstract]
    ABSTRACT: PURPOSE To extend CADx techniques for High Spectral and Spatial Resolution (HiSS) breast MRI, and to assess the ability of the Lorentzian-fit-subtraction residual maxima of the water resonance spectra to distinguish between benign and malignant breast tumors. METHOD AND MATERIALS HiSS high resolution spectroscopic MR images were collected under an IRB-approved protocol. To analyze HiSS data, we fit a Lorentzian curve to a 25 bin (140 Hz) region of the proton-resonance spectra in each lesion, centered at the water resonance and normalized to the water peak height. After subtracting this fit from each spectrum, the maximum residual value in nine spectral bins from +22.4 to +67.2 Hz to the high frequency side of the water peak was recorded. For each lesion, we calculated the average off-peak residual values within the upper 40% of the maximum residual in the entire lesion in order to eliminate voxels with off-peaks close to or below the noise floor. Using ROC analysis, the spectral bin-weighted average of the maxima in each lesion was evaluated using the clinical biopsied diagnosis (15 malignant; 8 benign cases) as truth, and the performance of this feature was assessed using the area under the ROC curve (AUC) as the figure of merit. RESULTS In the task of distinguishing between malignant and benign lesions, analysis of the bin-weighted maxima averages yielded an AUC value of 0.71 ± 0.11. CONCLUSION We have presented a technique utilizing a lesion-based approach to HiSS spectral analysis, with potential for use in the diagnosis of cancerous breast lesions. This is as an extension to previous work which developed a method of voxel-based classification, using analysis techniques similar to those presented here. CLINICAL RELEVANCE/APPLICATION A novel imaging marker can be derived from HiSS images, which is likely to be uncorrelated with other imaging markers, and thus may improve specificity of breast cancer MRI CADx.
    Radiological Society of North America 2012 Scientific Assembly and Annual Meeting; 11/2012
  • [Show abstract] [Hide abstract]
    ABSTRACT: PURPOSE Colon cancer is one of the most common forms of cancer and its early detection can vastly improve outcomes. MRI contrast agents can greatly improve diagnostic accuracy. Here we compare a new MRI contrast agent that is sensitive to glycolysis to a conventional Gd-based agent. Specifically, we report on: (1) MRI using Gd and a cancer specific, vanadium-based agent (VC) to measure contrast improvement in vivo, and (2) X-ray fluorescence microscopy (XFM) to quantify contrast uptake directly and to determine cellular and sub-cellular distributions in situ. METHOD AND MATERIALS Colonic tumors were induced in CF1 female mice (n=25) with i.p. injection of azoxymethane weekly for 2 weeks (10 mg/kg), followed by 2 cycles of 2.5% dextran sulfate sodium in the drinking water for 5 days. This model mimics many clinical and pathological features of colitis-associated colon cancer. T1/T2*-weighted and contrast-enhanced MR images were acquired using a 9.4T Bruker scanner. The day after the last in vivo MRI, mice were sacrificed after Gd and/or VC injection I.V. (0.13 mmol/kg), colons (normal and tumors) were harvested and ~5 μm slices were sectioned for XFM and H&E. XFM images were acquired using an X-ray microprobe at the Argonne Natl Lab. Concentrations of metal ions and other elements were determined based on the tissue thickness on the XFM slide. RESULTS Values of T2 distinguished normal colon from colonic wall focally thickened with tumor (p<0.005). From DCEMRI, the values of Ktrans (min-1) were found to be 0.12±0.01 for normal colon and 0.61±0.05 for tumors (p<0.001). For VC uptake in implanted rodent tumors, peak enhancements in tumor and muscle of 0.225 ± 0.052 and 0.05 ± 0.018, respectively, were measured during the injection phase - a nearly 5-fold increase in enhancement between tumor and muscle with p < 0.001. XFM studies of normal and colon cancer-bearing mice suggest specific uptake of VC in tumor regions, while Gd distributes uniformly. High-resolution (0.3 micron) scans of tumors revealed that the uptake of VC in cancer cells is ~8-fold higher compared to the background VC signal. CONCLUSION VC-based agents preferentially accumulate in cancer cells, offering an advantage over less selective Gd-based agents. CLINICAL RELEVANCE/APPLICATION VCs accumulate selectively in tumors - improve cancer diagnosis and staging. MRI and XFM studies of early colon cancer in mice may improve new information regarding cancer progression and therapies.
    Radiological Society of North America 2012 Scientific Assembly and Annual Meeting; 11/2012

Publication Stats

2k Citations
321.61 Total Impact Points

Institutions

  • 1996–2015
    • University of Chicago
      • Department of Radiology
      Chicago, Illinois, United States
  • 1996–2014
    • The University of Chicago Medical Center
      • Department of Radiology
      Chicago, Illinois, United States
  • 1997–2013
    • University of Illinois at Chicago
      • • Department of Radiology (Chicago)
      • • Department of Medicine (Chicago)
      Chicago, Illinois, United States