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Diffusion-Weighted Intravoxel Incoherent Motion Imaging of Renal Tumors With Histopathologic Correlation
Chandarana, Hersh; Kang, Stella K; Wong, Samson; Rusinek, Henry; Zhang, Jeff L; Arizono, Shigeki; Huang, William C; Melamed, Jonathan; Babb, James S; Suan, Edgar F; Lee, Vivian S; Sigmund, Eric E
PURPOSE: The aim of this study was to use intravoxel incoherent motion diffusion-weighted imaging to discriminate subtypes of renal neoplasms and to assess agreement between intravoxel incoherent motion (perfusion fraction, fp) and dynamic contrast-enhanced magnetic resonance imaging (MRI) metrics of tumor vascularity. SUBJECTS AND METHODS: In this Health Insurance Portability and Accountability Act-compliant, institutional review board-approved prospective study, 26 patients were imaged at 1.5-T MRI using dynamic contrast-enhanced MRI with high temporal resolution and diffusion-weighted imaging using 8 b values (range, 0-800 s/mm). Perfusion fraction (fp), tissue diffusivity (Dt), and pseudodiffusivity (Dp) were calculated using biexponential fitting of the diffusion data. Apparent diffusion coefficient (ADC) was calculated with monoexponential fit using 3 b values of 0, 400, and 800 s/mm. Dynamic contrast-enhanced data were processed with a semiquantitative method to generate model-free parameter cumulative initial area under the curve of gadolinium concentration at 60 seconds (CIAUC60). Perfusion fraction, Dt, Dp, ADC, and CIAUC60 were compared between different subtypes of renal lesions. Perfusion fraction was correlated with CIAUC60. RESULTS: We examined 14 clear cell, 4 papillary, 5 chromophobe, and 3 cystic renal cell carcinomas (RCCs). Although fp had higher accuracy (area under the curve, 0.74) for a diagnosis of clear cell RCC compared with Dt or ADC, the combination of fp and Dt had the highest accuracy (area under the curve, 0.78). The combination of fp and Dt diagnosed papillary RCC and cystic RCC with 100% accuracy, and clear cell RCC and chromophobe RCC, with 86.5% accuracy. There was significant strong correlation between fp and CIAUC60 (r = 0.82; P < 0.001). CONCLUSION: Intravoxel incoherent motion parameters fp and Dt can discriminate renal tumor subtypes. Perfusion fraction demonstrates good correlation with CIAUC60 and can assess degree of tumor vascularity without the use of exogenous contrast agent.
PMID: 22996315
ISSN: 0020-9996
CID: 179984
High-resolution human cervical spinal cord imaging at 7 T
Sigmund, E E; Suero, G A; Hu, C; McGorty, K; Sodickson, D K; Wiggins, G C; Helpern, J A
We present high-resolution anatomical imaging of the cervical spinal cord in healthy volunteers at the ultrahigh field of 7 T with a prototype four-channel radiofrequency coil array, in comparison with 3-T imaging of the same subjects. Signal-to-noise ratios at both field strengths were estimated using the rigorous Kellman method. Spinal cord cross-sectional area measurements were performed, including whole-cord measurements at both fields and gray matter segmentation at 7 T. The 7-T array coil showed reduced sagittal coverage, comparable axial coverage and the expected significantly higher signal-to-noise ratio compared with equivalent 3-T protocols. In the cervical spinal cord, the signal-to-noise ratio was found by the Kellman method to be higher by a factor of 3.5 with the 7-T coil than with standard 3-T coils. Cervical spine imaging in healthy volunteers at 7 T revealed not only detailed white/gray matter differentiation, but also structures not visualized at lower fields, such as denticulate ligaments, nerve roots and rostral-caudal blood vessels. Whole-cord cross-sectional area measurements showed good agreement at both field strengths. The measurable gray/white matter cross-sectional areas at 7 T were found to be comparable with reports from histology. These pilot data demonstrate the use of higher signal-to-noise ratios at the ultrahigh field of 7 T for significant improvement in anatomical resolution of the cervical spinal cord, allowing the visualization of structures not seen at lower field strength, particularly for axial imaging
PMCID:3377161
PMID: 22183956
ISSN: 0952-3480
CID: 169467
Prostate Cancer: Feasibility and Preliminary Experience of a Diffusional Kurtosis Model for Detection and Assessment of Aggressiveness of Peripheral Zone Cancer
Rosenkrantz, AB; Sigmund, EE; Johnson, G; Babb, JS; Mussi, TC; Melamed, J; Taneja, SS; Lee, VS; Jensen, JH
Purpose: To assess the feasibility of diffusional kurtosis (DK) imaging for distinguishing benign from malignant regions, as well as low- from high-grade malignant regions, within the peripheral zone (PZ) of the prostate in comparison with standard diffusion-weighted (DW) imaging. Materials and Methods: The institutional review board approved this retrospective HIPAA-compliant study and waived informed consent. Forty-seven patients with prostate cancer underwent 3-T magnetic resonance imaging by using a pelvic phased-array coil and DW imaging (maximum b value, 2000 sec/mm(2)). Parametric maps were obtained for apparent diffusion coefficient (ADC); the metric DK (K), which represents non-Gaussian diffusion behavior; and corrected diffusion (D) that accounts for this non-Gaussianity. Two radiologists reviewed these maps and measured ADC, D, and K in sextants positive for cancer at biopsy. Data were analyzed by using mixed-model analysis of variance and receiver operating characteristic curves. Results: Seventy sextants exhibited a Gleason score of 6; 51 exhibited a Gleason score of 7 or 8. K was significantly greater in cancerous sextants than in benign PZ (0.96 ± 0.24 vs 0.57 ± 0.07, P < .001), as well as in cancerous sextants with higher rather than lower Gleason score (1.05 ± 0.26 vs 0.89 ± 0.20, P < .001). K showed significantly greater sensitivity for differentiating cancerous sextants from benign PZ than ADC or D (93.3% vs 78.5% and 83.5%, respectively; P < .001), with equal specificity (95.7%, P > .99). K exhibited significantly greater sensitivity for differentiating sextants with low- and high-grade cancer than ADC or D (68.6% vs 51.0% and 49.0%, respectively; P ≤ .004) but with decreased specificity (70.0% vs 81.4% and 82.9%, respectively; P ≤ .023). K had significantly greater area under the curve for differentiating sextants with low- and high-grade cancer than ADC (0.70 vs 0.62, P = .010). Relative contrast between cancerous sextants and benign PZ was significantly greater for D or K than ADC (0.25 ± 0.14 and 0.24 ± 0.13, respectively, vs 0.18 ± 0.10; P < .001). Conclusion: Preliminary findings suggest increased value for DK imaging compared with standard DW imaging in prostate cancer assessment. Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12112290/-/DC1
PMID: 22550312
ISSN: 0033-8419
CID: 167146
Intravoxel Incoherent Motion and Diffusion-Tensor Imaging in Renal Tissue under Hydration and Furosemide Flow Challenges
Sigmund, EE; Vivier, PH; Sui, D; Lamparello, NA; Tantillo, K; Mikheev, A; Rusinek, H; Babb, JS; Storey, P; Lee, VS; Chandarana, H
Purpose:To assess the reproducibility and the distribution of intravoxel incoherent motion (IVIM) and diffusion-tensor (DT) imaging parameters in healthy renal cortex and medulla at baseline and after hydration or furosemide challenges.Materials and Methods:Using an institutional review board-approved HIPAA-compliant protocol with written informed consent, IVIM and DT imaging were performed at 3 T in 10 volunteers before and after water loading or furosemide administration. IVIM (apparent diffusion coefficient [ADC], tissue diffusivity [D(t)], perfusion fraction [f(p)], pseudodiffusivity [D(p)]) and DT (mean diffusivity [MD], fractional anisotropy [FA], eigenvalues [lambda(i)]) imaging parameters and urine output from serial bladder volumes were calculated. (a) Reproducibility was quantified with coefficient of variation, intraclass correlation coefficient, and Bland-Altman limits of agreement; (b) contrast and challenge response were quantified with analysis of variance; and (c) Pearson correlations were quantified with urine output.Results:Good reproducibility was found for ADC, D(t), MD, FA, and lambda(i) (average coefficient of variation, 3.7% [cortex] and 5.0% [medulla]), and moderate reproducibility was found for D(p), f(p), and f(p) . D(p) (average coefficient of variation, 18.7% [cortex] and 25.9% [medulla]). Baseline cortical diffusivities significantly exceeded medullary values except D(p), for which medullary values significantly exceeded cortical values, and lambda(1,) which showed no contrast. ADC, D(t), MD, and lambda(i) increased significantly for both challenges. Medullary diffusivity increases were dominated by transverse diffusion (1.72 +/- 0.09 [baseline] to 1.79 +/- 0.10 [hydration] mum(2)/msec, P = .0059; or 1.86 +/- 0.07 [furosemide] mum(2)/msec, P = .0094). Urine output correlated with cortical ADC with furosemide (r = 0.7, P = .034) and with medullary lambda(1) (r = 0.83, P = .0418), lambda(2) (r = 0.85, P = .0301), and MD (r = 0.82, P = .045) with hydration.Conclusion:Diffusion MR metrics are sensitive to flow changes in kidney induced by diuretic challenges. The results of this study suggest that vascular flow, tubular dilation, water reabsorption, and intratubular flow all play important roles in diffusion-weighted imaging contrast.(c) RSNA, 2012.
PMID: 22523327
ISSN: 0033-8419
CID: 167147
A versatile flow phantom for intravoxel incoherent motion MRI
Cho GY; Kim S; Jensen JH; Storey P; Sodickson DK; Sigmund EE
Although there have been many advancements in cancer research, much is still unknown about the heterogeneous tumor microenvironment. Diffusion-weighted MRI has proven to be a viable and versatile microstructural probe. Diffusion-weighted sequences specifically sensitive to intravoxel incoherent motion (IVIM) have seen a recent resurgence of interest as they promise to provide a valuable window on the vascular microenvironment. To understand, test, and optimize IVIM-sensitive approaches, a complex flow phantom was constructed to mimic certain characteristics of the tumor microenvironment such as tortuous microvasculature, heterogeneous vascular permeability, and interstitial fluid pressure buildup. Results using this phantom on a clinical scanner platform confirmed IVIM sensitivity to microscopic flow effects. Biexponential fitting of signal decay curves enabled quantitative extraction of perfusion fraction, IVIM-related pseudodiffusivity, and tissue diffusivity. Parametric maps were also generated, illustrating the potential utility of IVIM-sensitive imaging in clinical settings. The flow phantom proved to be an effective test-bed for validating and optimizing the IVIM-MRI technique to provide surrogate markers for microvascular properties. Magn Reson Med, 2011. (c) 2011 Wiley Periodicals, Inc
PMID: 22114007
ISSN: 1522-2594
CID: 149836
Interstitial fluid pressure correlates with intravoxel incoherent motion imaging metrics in a mouse mammary carcinoma model
Kim, S; Decarlo, L; Cho, GY; Jensen, JH; Sodickson, DK; Moy, L; Formenti, S; Schneider, RJ; Goldberg, JD; Sigmund, EE
The effective delivery of a therapeutic drug to the core of a tumor is often impeded by physiological barriers, such as the interstitial fluid pressure (IFP). There are a number of therapies that can decrease IFP and induce tumor vascular normalization. However, a lack of a noninvasive means to measure IFP hinders the utilization of such a window of opportunity for the maximization of the treatment response. Thus, the purpose of this study was to investigate the feasibility of using intravoxel incoherent motion (IVIM) diffusion parameters as noninvasive imaging biomarkers for IFP. Mice bearing the 4T1 mammary carcinoma model were studied using diffusion-weighted imaging (DWI), immediately followed by wick-in-needle IFP measurement. Voxelwise analysis was conducted with a conventional monoexponential diffusion model, as well as a biexponential model taking IVIM into account. There was no significant correlation of IFP with either the median apparent diffusion coefficient from the monoexponential model (r = 0.11, p = 0.78) or the median tissue diffusivity from the biexponential model (r = 0.30, p = 0.44). However, IFP was correlated with the median pseudo-diffusivity (D(p) ) of apparent vascular voxels (r = 0.76, p = 0.02) and with the median product of the perfusion fraction and pseudo-diffusivity (f(p) D(p) ) of apparent vascular voxels (r = 0.77, p = 0.02). Although the effect of IVIM in tumors has been reported previously, to our knowledge, this study represents the first direct comparison of IVIM metrics with IFP, with the results supporting the feasibility of the use of IVIM DWI metrics as noninvasive biomarkers for tumor IFP
PMCID:3883504
PMID: 22072561
ISSN: 0952-3480
CID: 160660
Magnetic Resonance Characterization of Porous Media Using Diffusion through Internal Magnetic Fields
Cho, Hyung Joon; Sigmund, Eric E; Song, Yiqiao
When a porous material is inserted into a uniform magnetic field, spatially varying fields typically arise inside the pore space due to susceptibility contrast between the solid matrix and the surrounding fluid. As a result, direct measurement of the field variation may provide a unique opportunity to characterize the pore geometry. The sensitivity of nuclear magnetic resonance (NMR) to inhomogeneous field variations through their dephasing effects on diffusing spins is unique and powerful. Recent theoretical and experimental research sheds new light on how to utilize susceptibility-induced internal field gradients to quantitatively probe the microstructure of porous materials. This article reviews ongoing developments based on the stimulated echo-pulse sequence to extend the characterization of porous media using both spatially resolved and unresolved susceptibility-induced internal gradients that operate on a diffusing-spin ensemble.
PMCID:5448962
PMID: 28816998
ISSN: 1996-1944
CID: 3069742
Optimization of b-value sampling for diffusion-weighted imaging of the kidney
Zhang JL; Sigmund EE; Rusinek H; Chandarana H; Storey P; Chen Q; Lee VS
Diffusion-weighted imaging (DWI) involves data acquisitions at multiple b values. In this paper, we presented a method of selecting the b values that maximize estimation precision of the biexponential analysis of renal DWI data. We developed an error propagation factor for the biexponential model, and proposed to optimize the b-value samplings by minimizing the error propagation factor. A prospective study of four healthy human subjects (eight kidneys) was done to verify the feasibility of the proposed protocol and to assess the validity of predicted precision for DWI measures, followed by Monte Carlo simulations of DWI signals based on acquired data from renal lesions of 16 subjects. In healthy subjects, the proposed methods improved precision (P = 0.003) and accuracy (P < 0.001) significantly in region-of-interest based biexponential analysis. In Monte Carlo simulation of renal lesions, the b-sampling optimization lowered estimation error by at least 20-30% compared with uniformly distributed b values, and improved the differentiation between malignant and benign lesions significantly. In conclusion, the proposed method has the potential of maximizing the precision and accuracy of the biexponential analysis of renal DWI. Magn Reson Med, 2011. (c) 2011 Wiley-Liss, Inc
PMCID:5088264
PMID: 21702062
ISSN: 1522-2594
CID: 135366
Diffusion-weighted imaging of the brain at 7 T with echo-planar and turbo spin echo sequences: preliminary results
Sigmund, Eric E; Gutman, David
Ultra-high-field clinical MRI scanners (e.g., 7 T and above) are becoming increasingly prevalent and can potentially enhance diagnostic ability through higher contrast, resolution and/or sensitivity. Diffusion-weighted MRI is a highly valued component in today's radiological exam and may benefit from the enhanced signal-to-noise ratio provided by high field with the appropriate imaging strategy. The most common diffusion pulse sequence readout (echo-planar imaging (EPI)) has been widely employed for in vivo human 7 T diffusion tensor imaging (DTI). In this article, we present results of brain DTI at 7 T with two diffusion-weighted imaging pulse sequence readouts: echo-planar imaging (EPI-DTI) and turbo spin echo (TSE-DTI). Results indicate that analogous coverage, quality and resolution typical of lower field (2 mm) can be obtained by properly processed EPI-DTI at 7 T, and, with some reduction in efficiency and sharpness, TSE-DTI at 7 T. Furthermore, 7 T TSE-DTI shows promise in obtaining higher-resolution results in targeted acquisitions of specific brain areas
PMID: 21550741
ISSN: 1873-5894
CID: 135530
Intravoxel incoherent motion imaging of tumor microenvironment in locally advanced breast cancer
Sigmund, E E; Cho, G Y; Kim, S; Finn, M; Moccaldi, M; Jensen, J H; Sodickson, D K; Goldberg, J D; Formenti, S; Moy, L
Diffusion-weighted imaging plays important roles in cancer diagnosis, monitoring, and treatment. Although most applications measure restricted diffusion by tumor cellularity, diffusion-weighted imaging is also sensitive to vascularity through the intravoxel incoherent motion effect. Hypervascularity can confound apparent diffusion coefficient measurements in breast cancer. We acquired multiple b-value diffusion-weighted imaging at 3 T in a cohort of breast cancer patients and performed biexponential intravoxel incoherent motion analysis to extract tissue diffusivity (D(t) ), perfusion fraction (f(p) ), and pseudodiffusivity (D(p) ). Results indicated significant differences between normal fibroglandular tissue and malignant lesions in apparent diffusion coefficient mean (+/-standard deviation) values (2.44 +/- 0.30 vs. 1.34 +/- 0.39 mum(2) /msec, P < 0.01) and D(t) (2.36 +/- 0.38 vs. 1.15 +/- 0.35 mum(2) /msec, P < 0.01). Lesion diffusion-weighted imaging signals demonstrated biexponential character in comparison to monoexponential normal tissue. There is some differentiation of lesion subtypes (invasive ductal carcinoma vs. other malignant lesions) with f(p) (10.5 +/- 5.0% vs. 6.9 +/- 2.9%, P = 0.06), but less so with D(t) (1.14 +/- 0.32 mum(2) /msec vs. 1.18 +/- 0.52 mum(2) /msec, P = 0.88) and D(p) (14.9 +/- 11.4 mum(2) /msec vs. 16.1 +/- 5.7 mum(2) /msec, P = 0.75). Comparison of intravoxel incoherent motion biomarkers with contrast enhancement suggests moderate correlations. These results suggest the potential of intravoxel incoherent motion vascular and cellular biomarkers for initial grading, progression monitoring, or treatment assessment of breast tumors. Magn Reson Med, 2011. (c) 2011 Wiley-Liss, Inc
PMCID:4692245
PMID: 21287591
ISSN: 1522-2594
CID: 131795