Eric E. Sigmund

Diagnosis of cirrhosis with intravoxel incoherent motion diffusion MRI and dynamic contrast-enhanced MRI alone and in combination: preliminary experience.

To report our preliminary experience with the use of intravoxel incoherent motion (IVIM) diffusion‐weighted magnetic resonance imaging (DW‐MRI) and dynamic contrast‐enhanced (DCE)‐MRI alone and in combination for the diagnosis of liver cirrhosis.

Prostate Cancer: Feasibility and Preliminary Experience of a Diffusional Kurtosis Model for Detection and Assessment of Aggressiveness of Peripheral Zone Cancer

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/mm2). 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.

Comparison of biexponential and monoexponential model of diffusion weighted imaging in evaluation of renal lesions: preliminary experience.

Objectives:To obtain intravoxel incoherent motion (IVIM) parameters with biexponential analysis of multiple b-value diffusion-weighted imaging (DWI) and compare these parameters to apparent diffusion coefficient (ADC) obtained with monoexponential modeling in their ability to discriminate enhancing from nonenhancing renal lesions. Materials and Methods:Twenty-eight patients were imaged at 1.5 T utilizing contrast-enhanced (CE) magnetic resonance imaging (MRI) and breath-hold DWI using 8 b values (range: 0–800 s/mm2). Perfusion fraction (fp), tissue diffusivity (Dt), and pseudo-diffusion coefficient (Dp) were calculated using segmented biexponential analysis. ADCtotal and ADC0–400–800 were calculated with monoexponential fitting of the DWI data. fp, Dt, Dp, ADCtotal, and ADC0–400–800 were compared between enhancing and nonenhancing renal lesions. Receiver operating characteristic analysis was performed for all DWI parameters. fp was correlated with percent enhancement. Results:There were a total of 31 renal lesions (15 enhancing and 16 nonenhancing) in 28 patients on CE-MRI. fp of enhancing masses was significantly higher (27.9 vs. 6.1) and Dt was significantly lower (1.47 vs. 2.40 ×10−3 mm2/s). IVIM parameters fp and Dt demonstrated higher accuracy in differentiating enhancing from nonenhancing renal lesions compared with monoexponential parameters ADC0–400–800 and ADCtotal, with area under the curve of 0.946, 0.896, 0.854, and 0.675, respectively. There was a good correlation between fp and percent enhancement (r = 0.7; P < 0.001). Conclusion:IVIM parameters fp and Dt obtained with biexponential fitting of multi-b value DWI have higher accuracy compared with ADC (obtained with monoexponential fit) in discriminating enhancing from nonenhancing renal lesions. Furthermore, fp demonstrates good correlation with percent enhancement and can provide information regarding lesion vascularity without the use of exogenous contrast agent.

Intravoxel Incoherent Motion and Diffusion-Tensor Imaging in Renal Tissue under Hydration and Furosemide Flow Challenges

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 [λ(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 λ(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 λ(1,) which showed no contrast. ADC, D(t), MD, and λ(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] μm(2)/msec, P = .0059; or 1.86 ± 0.07 [furosemide] μm(2)/msec, P = .0094). Urine output correlated with cortical ADC with furosemide (r = 0.7, P = .034) and with medullary λ(1) (r = 0.83, P = .0418), λ(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.

Intravoxel incoherent motion imaging of tumor microenvironment in locally advanced breast cancer

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 (Dt), perfusion fraction (fp), and pseudodiffusivity (Dp). 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 μm2/msec, P < 0.01) and Dt (2.36 ± 0.38 vs. 1.15 ± 0.35 μm2/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 fp (10.5 ± 5.0% vs. 6.9 ± 2.9%, P = 0.06), but less so with Dt (1.14 ± 0.32 μm2/msec vs. 1.18 ± 0.52 μm2/msec, P = 0.88) and Dp (14.9 ± 11.4 μm2/msec vs. 16.1 ± 5.7 μm2/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.

T1 Hyperintense Renal Lesions: Characterization with Diffusion-weighted MR Imaging versus Contrast-enhanced MR Imaging

PURPOSE To compare the performance of apparent diffusion coefficient (ADC) measurement obtained with diffusion-weighted (DW) magnetic resonance (MR) imaging in the characterization of non-fat-containing T1 hyperintense renal lesions with that of contrast material-enhanced MR imaging, with histopathologic analysis and follow-up imaging as the reference standards. MATERIALS AND METHODS Institutional review board approval was obtained for this HIPAA-compliant retrospective study, and the informed consent requirement was waived. Two independent observers retrospectively assessed MR images obtained in 41 patients with non-fat-containing T1 hyperintense renal lesions. The MR examination included acquisition of DW and contrast-enhanced T1-weighted images. For each index lesion, the observers assessed the (a) mean (+/- standard deviation) of ADC, (b) enhancement ratio, and (c) subtracted images for the presence of enhancement (confidence score, 1-5). Histopathologic analysis of renal cell carcinomas (RCCs) and follow-up imaging for benign lesions were the reference standards. ADCs of benign lesions and RCCs were compared. Receiver operating characteristic (ROC) curve analysis was performed to assess the accuracy of DW imaging, enhancement ratio, and subtraction for the diagnosis of RCC. RESULTS A total of 64 lesions (mean diameter, 3.9 cm), including 38 benign T1 hyperintense cysts and 26 RCCs, were assessed. Mean ADCs of RCCs were significantly lower than those of benign cysts ([1.75 +/- 0.57] x 10(-3) mm(2)/sec vs [2.50 +/- 0.53] x 10(-3) mm(2)/sec, P < .0001). ADCs of solid and cystic portions of complex cystic RCCs were significantly different ([1.37 +/- 0.55] x 10(-3) mm(2)/sec vs [2.45 +/- 0.63] x 10(-3) mm(2)/sec, P < .0001). When data from both observers were pooled, area under the ROC curve, sensitivity, and specificity were 0.846, 71%, and 91%, respectively, for DW imaging; 0.865, 65%, and 96%, respectively, for enhancement ratio (at the excretory phase); and 0.861, 83%, and 89%, respectively, for subtraction (P = .48 and P = .85, respectively). The combination of DW imaging and subtraction resulted in area under the ROC curve, sensitivity, and specificity of 0.893, 87%, and 92%, respectively, with significantly improved reader confidence compared with subtraction alone (P = .041). CONCLUSION The performance of DW imaging was equivalent to that of enhancement ratio in the characterization of T1 hyperintense renal lesions, with both methods having lower sensitivity than image subtraction without reaching significance.

Optimization of b-value sampling for diffusion-weighted imaging of the kidney

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.

Diffusion-weighted intravoxel incoherent motion imaging of renal tumors with histopathologic correlation

PurposeThe 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 MethodsIn 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/mm2). 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/mm2. 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. ResultsWe 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). ConclusionIntravoxel 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.

Assessment of hepatocellular carcinoma using apparent diffusion coefficient and diffusion kurtosis indices: preliminary experience in fresh liver explants.

OBJECTIVES The objective was to perform ex vivo evaluation of non-Gaussian diffusion kurtosis imaging (DKI) for assessment of hepatocellular carcinoma (HCC), including presence of treatment-related necrosis, using fresh liver explants. METHODS Twelve liver explants underwent 1.5-T magnetic resonance imaging using a DKI sequence with maximal b-value of 2000 s/mm(2). A standard monoexponential fit was used to calculate apparent diffusion coefficient (ADC), and a non-Gaussian kurtosis fit was used to calculate K, a measure of excess kurtosis of diffusion, and D, a corrected diffusion coefficient accounting for this non-Gaussian behavior. The mean value of these parameters was measured for 16 HCCs based upon histologic findings. For each metric, HCC-to-liver contrast was calculated, and coefficient of variation (CV) was computed for voxels within the lesion as an indicator of heterogeneity. A single hepatopathologist determined HCC necrosis and cellularity. RESULTS The 16 HCCs demonstrated intermediate-to-substantial excess diffusional kurtosis, and mean corrected diffusion coefficient D was 23% greater than mean ADC (P=.002). HCC-to-liver contrast and CV of HCC were greater for K than ADC or D, although these differences were significant only for CV of HCCs (P≤.046). ADC, D and K all showed significant differences between non-, partially and completely necrotic HCCs (P≤.004). Among seven nonnecrotic HCCs, cellularity showed a strong inverse correlation with ADC (r=-0.80), a weaker inverse correlation with D (-0.24) and a direct correlation with K (r=0.48). CONCLUSIONS We observed non-Gaussian diffusion behavior for HCCs ex vivo; this DKI model may have added value in HCC characterization in comparison with a standard monoexponential model of diffusion-weighted imaging.

Combined intravoxel incoherent motion and diffusion tensor imaging of renal diffusion and flow anisotropy.

We used a combined intravoxel incoherent motion–diffusion tensor imaging (IVIM‐DTI) methodology to distinguish structural from flow effects on renal diffusion anisotropy.