Faculty Bibliography

Purpose: Esophageal cancer patients undergoing radiotherapy usually receive daily or weekly cone-beam CT (CBCT) imaging to verify positioning before treatment. The purpose of this study is to evaluate the reproducibility of texture features extracted from CBCT and its correlation with CT features for their potential use as early predictors of esophageal cancer response during the course of RT. Methods: Ten patients treated for esophageal cancer that received daily CBCT were retrospectively evaluated (Varian TrueBeam with same Thorax imaging technique: half-fan, full-trajectory, 125 kVp, 270 mAs). The planning CT (CTP) and the two initial CBCTs (day 1 and 2 of treatment) were exported from Eclipse TPS to an in-house processing pipeline. This included edge detection for couch removal, CBCT resampling and automatic 3D rigid-registration of CBCT to CTP using Mattes mutual information metric. GTVs for each patient were exported and texture features were extracted from CTP and the registered CBCTs using the Imaging Biomarker Explorer (IBEX) software. Thirty-three texture features using cooccurrence and run-length matrices were extracted. Texture reproducibility between consecutive CBCTs was evaluated using intraclass correlation (ICC). CTP and CBCTs were evaluated using Pearson's correlation. Significance level was corrected for multiple testing using Bonferroni adjustment. Results: Registration results were deemed satisfactory using mutual information as well as visual inspection within the volume that encompassed the GTV. Out of the initial 33 texture features considered, 13 presented excellent (ICC > 0.9) reproducibility between the two initial CBCTs. Out of these 13 features, 5 presented statistically significant Pearson's correlation adjusted for multiple statistical tests (P < 0.004) ranging from 0.86 to 0.89 (Table). Conclusion: Several texture features from CBCT showed reproducibility between the first two days of treatment and strongly correlated between CTP and CBCT. Therefore, derived texture features could be investigated as predictors of treatment response during the course of treatment

OBJECTIVE:To explore the relationship between relative enhanced diffusivity (RED) and intravoxel incoherent motion (IVIM), as well as the impact of noise and the choice of intermediate diffusion weighting (b value) on the RED parameter. MATERIALS AND METHODS/METHODS:A mathematical derivation was performed to cast RED in terms of the IVIM parameters. Noise analysis and b value optimization was conducted by using Monte Carlo calculations to generate diffusion-weighted imaging data appropriate to breast and liver tissue at three different signal-to-noise ratios. RESULTS:RED was shown to be approximately linearly proportional to the IVIM parameter f, inversely proportional to D and to follow an inverse exponential decay with respect to D*. The choice of intermediate b value was shown to be important in minimizing the impact of noise on RED and in maximizing its discriminatory power. RED was shown to be essentially a reparameterization of the IVIM estimates for f and D obtained with three b values. CONCLUSION/CONCLUSIONS:, respectively. Future clinical studies involving RED should also estimate the IVIM parameters f and D using three b values for comparison.

PURPOSE:inhomogeneity-induced geometric distortion in echo-planar diffusion-weighted imaging on quantitative apparent diffusion coefficient (ADC) analysis in multiparametric prostate MRI. METHODS:-weighted images were mapped to the nondistortion-corrected and distortion-corrected data sets by resampling with and without spatial coregistration. The ADC values were calculated on the volume and voxel level. The effect of distortion correction on ADC quantification and tissue classification was evaluated using linear-mixed models and logistic regression, respectively. RESULTS:(voxel level)) between the nondistortion-corrected and distortion-corrected were significantly associated (P < 0.05) with distortion distance (mean: 1.4 ± 1.3 mm; range: 0.3-5.3 mm). No significant associations were found upon coregistration; however, in patients with high rectal gas residue, distortion correction resulted in improved spatial representation and significantly better classification of healthy versus tumor voxels (P < 0.05). CONCLUSIONS:Geometric distortion correction in DWI could improve quantitative ADC analysis in multiparametric prostate MRI. Magn Reson Med 79:2524-2532, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

BACKGROUND:Diffusion-weighted MRI (DWI) is currently one of the fastest developing MRI-based techniques in oncology. Histogram properties from model fitting of DWI are useful features for differentiation of lesions, and classification can potentially be improved by machine learning. PURPOSE:To evaluate classification of malignant and benign tumors and breast cancer subtypes using support vector machine (SVM). STUDY TYPE:Prospective. SUBJECTS:Fifty-one patients with benign (n = 23) and malignant (n = 28) breast tumors (26 ER+, whereof six were HER2+). FIELD STRENGTH/SEQUENCE:Patients were imaged with DW-MRI (3T) using twice refocused spin-echo echo-planar imaging with echo time / repetition time (TR/TE) = 9000/86 msec, 90 × 90 matrix size, 2 × 2 mm in-plane resolution, 2.5 mm slice thickness, and 13 b-values. ASSESSMENT:Apparent diffusion coefficient (ADC), relative enhanced diffusivity (RED), and the intravoxel incoherent motion (IVIM) parameters diffusivity (D), pseudo-diffusivity (D*), and perfusion fraction (f) were calculated. The histogram properties (median, mean, standard deviation, skewness, kurtosis) were used as features in SVM (10-fold cross-validation) for differentiation of lesions and subtyping. STATISTICAL TESTS:Accuracies of the SVM classifications were calculated to find the combination of features with highest prediction accuracy. Mann-Whitney tests were performed for univariate comparisons. RESULTS:For benign versus malignant tumors, univariate analysis found 11 histogram properties to be significant differentiators. Using SVM, the highest accuracy (0.96) was achieved from a single feature (mean of RED), or from three feature combinations of IVIM or ADC. Combining features from all models gave perfect classification. No single feature predicted HER2 status of ER + tumors (univariate or SVM), although high accuracy (0.90) was achieved with SVM combining several features. Importantly, these features had to include higher-order statistics (kurtosis and skewness), indicating the importance to account for heterogeneity. DATA CONCLUSION:Our findings suggest that SVM, using features from a combination of diffusion models, improves prediction accuracy for differentiation of benign versus malignant breast tumors, and may further assist in subtyping of breast cancer. LEVEL OF EVIDENCE:3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1205-1216.

BACKGROUND:Subject motion is known to produce spurious covariance among time-series in functional connectivity that has been reported to induce distance-dependent spurious correlations. PURPOSE/OBJECTIVE:To present a feasibility study for applying the extended Kalman filter (EKF) framework for high temporal resolution motion correction of resting state functional MRI (rs-fMRI) series using each simultaneous multi-slice (SMS) echo planar imaging (EPI) shot as its own navigator. STUDY TYPE/METHODS:Prospective feasibility study. POPULATION/SUBJECTS/UNASSIGNED:Three human volunteers. FIELD STRENGTH/SEQUENCE/UNASSIGNED:3T GE DISCOVERY MR750 scanner using a 32-channel head coil. Simultaneous multi-slice rs-fMRI sequence with repetition time (TR)/echo time (TE) = 800/30 ms, and SMS factor 6. ASSESSMENT/RESULTS:Motion estimates were computed using two techniques: a conventional rigid-body volume-wise registration; and a high-temporal resolution motion estimation rigid-body approach. The reference image was resampled using the estimates obtained from both approaches and the difference between these predicted volumes and the original moving series was summarized using the normalized mean squared error (NMSE). STATISTICAL TESTS/UNASSIGNED:Direct comparison of NMSE values. RESULTS:High-temporal motion estimation was always superior to volume-wise motion estimation for the sample presented. For staged continuous rotations, the NMSE using high-temporal resolution motion estimates ranged between [0.130, 0.150] for the first volunteer (in-plane rotations), between [0.060, 0.068] for the second volunteer (in-plane rotations), and between [0.063, 0.080] for the third volunteer (through-plane rotations). These values went up to [0.384, 0.464]; [0.136, 0.179]; and [0.080, 0.096], respectively, when using volume-wise motion estimates. DATA CONCLUSION/UNASSIGNED:Accurate high-temporal rigid-body motion estimates can be obtained for rs-fMRI taking advantage of simultaneous multi-slice EPI sub-TR shots. LEVEL OF EVIDENCE/METHODS:2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018.

PURPOSE/OBJECTIVE:To evaluate the diagnostic relevance of T2-weighted (T2W) MRI-derived textural features relative to quantitative physiological parameters derived from diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) MRI in Gleason score (GS) 3+4 and 4+3 prostate cancers. MATERIALS AND METHODS/METHODS:) were calculated from index tumours delineated on the T2W, DW, and DCE images, respectively. The association between the textural features and prostatectomy GS and the MRI-derived parameters, and the utility of the parameters in differentiating between GS 3+4 and 4+3 prostate cancers were assessed statistically. RESULTS:. The combined texture-MRI parameters yielded higher classification accuracy (91%) than the individual parameter sets. CONCLUSION/CONCLUSIONS:T2W MRI-derived textural features could serve as potential diagnostic markers, sensitive to the pathological differences in prostate cancers. KEY POINTS/CONCLUSIONS:• T2W MRI-derived textural features correlate significantly with Gleason score and ADC. • T2W MRI-derived textural features differentiate Gleason score 3+4 from 4+3 cancers. • T2W image textural features could augment tumour characterization.

PURPOSE: To explore the application of diffusion tensor imaging (DTI) for breast tissue and breast pathologies using a stimulated-echo acquisition mode (STEAM) with variable diffusion times. MATERIALS AND METHODS: In this Health Insurance Portability and Accountability Act-compliant study, approved by the local institutional review board, eight patients and six healthy volunteers underwent an MRI examination at 3 Tesla including STEAM-DTI with several diffusion times ranging from 68.5 to 902.5 ms. A DTI model was fitted to the data for each diffusion time, and parametric maps of mean diffusivity, fractional anisotropy, axial diffusivity, and radial diffusivity were computed for healthy fibroglandular tissue (FGT) and lesions. The median value of radial diffusivity for FGT was fitted to a linear decay to obtain an estimation of the surface-to-volume ratio, from which the radial diameter was calculated. RESULTS: For healthy FGT, radial diffusivity presented a linear decay with the square root of the diffusion time resulting in a range of estimated radial diameters from 202 to 496 microm, while axial diffusivity presented a nearly time-independent diffusion. Residual fat signal was reduced at longer diffusion times due to the shorter T1 of fat. Residual fat signal to the overall signal in the healthy volunteers' FGT was found to range from 2.39% to 2.55% (shortest mixing time), and from 0.40% to 0.51% (longest mixing time) for the b500 images. CONCLUSION: The use of variable diffusion times may provide an in vivo noninvasive tool to probe diffusion lengths in breast tissue and breast pathology, and might aid by improving fat suppression at longer diffusion times. J. Magn. Reson. Imaging 2016.

Purpose To evaluate the relative change of the apparent diffusion coefficient (ADC) at low- and medium-b-value regimens as a surrogate marker of microcirculation, to study its correlation with dynamic contrast agent-enhanced (DCE) magnetic resonance (MR) imaging-derived parameters, and to assess its potential for differentiation between malignant and benign breast tumors. Materials and Methods Ethics approval and informed consent were obtained. From May 2013 to June 2015, 61 patients diagnosed with either malignant or benign breast tumors were prospectively recruited. All patients were scanned with a 3-T MR imager, including diffusion-weighted imaging (DWI) and DCE MR imaging. Parametric analysis of DWI and DCE MR imaging was performed, including a proposed marker, relative enhanced diffusivity (RED). Spearman correlation was calculated between DCE MR imaging and DWI parameters, and the potential of the different DWI-derived parameters for differentiation between malignant and benign breast tumors was analyzed by dividing the sample into equally sized training and test sets. Optimal cut-off values were determined with receiver operating characteristic curve analysis in the training set, which were then used to evaluate the independent test set. Results RED had a Spearman rank correlation of 0.61 with the initial area under the curve calculated from DCE MR imaging. Furthermore, RED differentiated cancers from benign tumors with an overall accuracy of 90% (27 of 30) on the test set with 88.2% (15 of 17) sensitivity and 92.3% (12 of 13) specificity. Conclusion This study presents promising results introducing a simplified approach to assess results from a DWI protocol sensitive to the intravoxel incoherent motion effect by using only three b values. This approach could potentially aid in the differentiation, characterization, and monitoring of breast pathologies. ^© RSNA, 2016 Online supplemental material is available for this article.

PURPOSE/OBJECTIVE:To improve early diagnosis of prostate cancer to aid clinical decision-making. Diffusion-weighted magnetic resonance imaging (DW-MRI) is sensitive to water diffusion throughout tissues, which correlates with Gleason score, a histological measure of prostate cancer aggressiveness. In this study the ability of DW-MRI to detect prostate cancer onset and development was evaluated in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice. MATERIALS AND METHODS/METHODS:T2 -weighted and DW-MRI were acquired using a 7T MR scanner, 200 mm bore diameter; 10 TRAMP and 6 C57BL/6 control mice were scanned every 4 weeks from 8 weeks of age until sacrifice at 28-30 weeks. After sacrifice, the genitourinary tract was excised and sectioned for histological analysis. Histology slides registered with DW-MR images allowed for validation of DW-MR images and the apparent diffusion coefficient (ADC) as tools for cancer detection and disease stratification. An automated early assessment tool based on ADC threshold values was developed to aid cancer detection and progression monitoring. RESULTS:The ADC differentiated between control prostate ((1.86 ± 0.20) × 10(-3) mm(2) /s) and normal TRAMP prostate ((1.38 ± 0.10) × 10(-3) mm(2) /s) (P = 0.0001), between TRAMP prostate and well-differentiated cancer ((0.93 ± 0.18) × 10(-3) mm(2) /s) (P = 0.0006), and between well-differentiated cancer and poorly differentiated cancer ((0.63 ± 0.06) × 10(-3) mm(2) /s) (P = 0.02). CONCLUSION/CONCLUSIONS:DW-MRI is a tool for early detection of cancer, and discrimination between cancer stages in the TRAMP model. The incorporation of DW-MRI-based prostate cancer stratification and monitoring could increase the accuracy of preclinical trials using TRAMP mice.

BACKGROUND:To compare "standard" diffusion weighted imaging, and diffusion tensor imaging (DTI) of 2(nd) and 4(th) -order for the differentiation of malignant and benign breast lesions. METHODS:Seventy-one patients were imaged at 3 Tesla with a 16-channel breast coil. A diffusion weighted MRI sequence including b = 0 and b = 700 in 30 directions was obtained for all patients. The image data were fitted to three different diffusion models: isotropic model - apparent diffusion coefficient (ADC), 2(nd) -order tensor model (the standard model used for DTI) and a 4(th) -order tensor model, with increased degrees of freedom to describe anisotropy. The ability of the fitted parameters in the different models to differentiate between malignant and benign tumors was analyzed. RESULTS:Seventy-two breast lesions were analyzed, out of which 38 corresponded to malignant and 34 to benign tumors. ADC (using any model) presented the highest discriminative ability of malignant from benign tumors with a receiver operating characteristic area under the curve (AUC) of 0.968, and sensitivity and specificity of 94.1% and 94.7% respectively for a 1.33 × 10(-3) mm(2) /s cutoff. Anisotropy measurements presented high statistical significance between malignant and benign tumors (P < 0.001), but with lower discriminative ability of malignant from benign tumors than ADC (AUC of 0.896 and 0.897 for fractional anisotropy and generalized anisotropy respectively). Statistical significant difference was found between generalized anisotropy and fractional anisotropy for cancers (P < 0.001) but not for benign lesions (P = 0.87). CONCLUSION/CONCLUSIONS:While anisotropy parameters have the potential to provide additional value for breast applications as demonstrated in this study, ADC exhibited the highest differentiation power between malignant and benign breast tumors.