Faculty Bibliography

PURPOSE: To assess the diagnostic utility of contrast kinetic analysis for breast lesions and background parenchyma of women undergoing MRI-guided biopsies, for whom standard clinical analysis had failed to separate benign and malignant lesions. MATERIALS AND METHODS: This study included 115 women who had indeterminate lesions based on routine diagnostic breast MRI exams and underwent an MRI (3 Tesla) -guided biopsy of one or more lesions suspicious for breast cancer. Breast dynamic contrast-enhanced (DCE)-MRI was performed using a radial stack-of-stars three-dimensional spoiled gradient echo pulse sequence and modified k-space weighted image contrast image reconstruction. Contrast kinetic model analysis was conducted to characterize the contrast enhancement patterns measured in lesions and background parenchyma (BP). The transfer rate (Ktrans ), interstitial volume fraction (ve ), and vascular volume fraction (vp ) estimated from the lesion and BP were used to separate malignant from benign lesions. RESULTS: The patients with malignant lesions had significantly (P < 0.05) higher median lesion-Ktrans (0.081 min-1 ), higher median BP-Ktrans (0.032 min-1 ), and BP-vp (0.020) than those without malignant lesions (0.056 min-1 , 0.017 min-1 and 0.012, respectively). The area under the receiver operating characteristic curve (AUC) of the BP-Ktrans (0.687) was highest among the single parameters and higher than that of the lesion-Ktrans (0.664). The combined logistic regression model of lesion-Ktrans , lesion-ve , BP-Ktrans , BP-ve , and BP-vp had the highest AUC of 0.730. CONCLUSION: Our results suggest that the contrast kinetic analysis of DCE-MRI data can be used to differentiate the malignant lesions from the benign and high-risk lesions among the indeterminate breast lesions recommended for MRI-guided biopsy exams. LEVEL OF EVIDENCE: 3 J. Magn. Reson. Imaging 2016.

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.

Solid tumor microstructure is related to the aggressiveness of the tumor, interstitial pressure and drug delivery pathways, which are closely associated with treatment response, metastatic spread and prognosis. In this study, we introduce a novel diffusion MRI data analysis framework, pulsed and oscillating gradient MRI for assessment of cell size and extracellular space (POMACE), and demonstrate its feasibility in a mouse tumor model. In vivo and ex vivo POMACE experiments were performed on mice bearing the GL261 murine glioma model (n = 8). Since the complete diffusion time dependence is in general non-analytical, the tumor microstructure was modeled in an appropriate time/frequency regime by impermeable spheres (radius Rcell , intracellular diffusivity Dics ) surrounded by extracellular space (ECS) (approximated by constant apparent diffusivity Decs in volume fraction ECS). POMACE parametric maps (ECS, Rcell , Dics , Decs ) were compared with conventional diffusion-weighted imaging metrics, electron microscopy (EM), alternative ECS determination based on effective medium theory (EMT), and optical microscopy performed on the same samples. It was shown that Decs can be approximated by its long time tortuosity limit in the range [1/(88 Hz)-31 ms]. ECS estimations (44 +/- 7% in vivo and 54 +/- 11% ex vivo) were in agreement with EMT-based ECS and literature on brain gliomas. Ex vivo, ECS maps correlated well with optical microscopy. Cell sizes (Rcell = 4.8 +/- 1.3 in vivo and 4.3 +/- 1.4 microm ex vivo) were consistent with EM measurements (4.7 +/- 1.8 microm). In conclusion, Rcell and ECS can be quantified and mapped in vivo and ex vivo in brain tumors using the proposed POMACE method. Our experimental results support the view that POMACE provides a way to interpret the frequency or time dependence of the diffusion coefficient in tumors in terms of objective biophysical parameters of neuronal tissue, which can be used for non-invasive monitoring of preclinical cancer studies and treatment efficacy

Purpose To demonstrate the feasibility of the use of a rapid, noninvasive, in vivo imaging method to measure fatty acid fractions of breast adipose tissue during diagnostic breast magnetic resonance (MR) examinations and to investigate associations between fatty acid fractions in breast adipose tissue and breast cancer status by using this method. Materials and Methods The institutional review board approved this retrospective HIPAA-compliant study and informed consent was waived. Between July 2013 and September 2014, multiple-echo three-dimensional gradient-echo data were acquired for 89 women. Spectra were generated and used to estimate fractions of monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), and saturated fatty acid (SFA) in the breast adipose tissue. Analysis of covariance and exact Mann-Whitney tests were used to compare groups and the Spearman rank correlation coefficient was used to characterize the association of each imaging measure with each attribute. Results For postmenopausal women, MUFA was lower (0.38 +/- 0.06 vs 0.46 +/- 0.10; P < .05) and SFA was higher (0.31 +/- 0.07 vs 0.19 +/- 0.11; P < .05) for women with invasive ductal carcinoma than for those with benign tissue. No correlation was found between body mass index (BMI) and fatty acid fractions in breast adipose tissue. In women with benign tissue, postmenopausal women had a higher PUFA (0.35 +/- 0.06 vs 0.27 +/- 0.05; P < .01) and lower SFA (0.19 +/- 0.11 vs 0.30 +/- 0.12; P < .05) than premenopausal women. Conclusion There is a possible link between the presence of invasive ductal carcinoma and fatty acid fractions in breast adipose tissue for postmenopausal women in whom BMI values are not correlated with the fatty acid fractions. (c) RSNA, 2016 Online supplemental material is available for this article.

Purpose To compare fluorine 18 (18F) fluorodeoxyglucose (FDG) combined positron emission tomography (PET) and magnetic resonance (MR) imaging with 18F FDG combined PET and computed tomography (CT) in terms of organ-specific metastatic lesion detection and radiation dose in patients with breast cancer. Materials and Methods From July 2012 to October 2013, this institutional review board-approved HIPAA-compliant prospective study included 51 patients with breast cancer (50 women; mean age, 56 years; range, 32-76 years; one man; aged 70 years) who completed PET/MR imaging with diffusion-weighted and contrast material-enhanced sequences after unenhanced PET/CT. Written informed consent for study participation was obtained. Two independent readers for each modality recorded site and number of lesions. Imaging and clinical follow-up, with consensus in two cases, served as the reference standard. Results There were 242 distant metastatic lesions in 30 patients, 18 breast cancers in 17 patients, and 19 positive axillary nodes in eight patients. On a per-patient basis, PET/MR imaging with diffusion-weighted and contrast-enhanced sequences depicted distant (30 of 30 [100%] for readers 1 and 2) and axillary (eight of eight [100%] for reader 1, seven of eight [88%] for reader 2) metastatic disease at rates similar to those of unenhanced PET/CT (distant metastatic disease: 28 of 29 [96%] for readers 3 and 4, P = .50; axillary metastatic disease: seven of eight [88%] for readers 3 and 4, P > .99) and outperformed PET/CT in the detection of breast cancer (17 of 17 [100%] for readers 1 and 2 vs 11 of 17 [65%] for reader 3 and 10 of 17 [59%] for reader 4; P < .001). PET/MR imaging showed increased sensitivity for liver (40 of 40 [100%] for reader 1 and 32 of 40 [80%] for reader 2 vs 30 of 40 [75%] for reader 3 and 28 of 40 [70%] for reader 4; P < .001) and bone (105 of 107 [98%] for reader 1 and 102 of 107 [95%] for reader 2 vs 106 of 107 [99%] for reader 3 and 93 of 107 [87%] for reader 4; P = .012) metastases and revealed brain metastases in five of 51 (10%) patients. PET/CT trended toward increased sensitivity for lung metastases (20 of 23 [87%] for reader 1 and 17 of 23 [74%] for reader 2 vs 23 of 23 [100%] for reader 3 and 22 of 23 [96%] for reader 4; P = .065). Dose reduction averaged 50% (P < .001). Conclusion In patients with breast cancer, PET/MR imaging may yield better sensitivity for liver and possibly bone metastases but not for pulmonary metastases, as compared with that attained with PET/CT, at about half the radiation dose. (c) RSNA, 2016 Online supplemental material is available for this article.

PURPOSE: This study aims to investigate the feasibility of using simultaneous breast MRI and PET to assess the synergy of MR pharmacokinetic and fluorine-18 fluorodeoxyglucose (F-FDG) uptake data to characterize tumor aggressiveness in terms of metastatic burden and Ki67 status. METHODS: Twelve consecutive patients underwent breast and whole-body PET/MRI. During the MR scan, PET events were simultaneously accumulated. MR contrast kinetic model parametric maps were computed using the extended Tofts model, including the volume transfer constant between blood plasma and the interstitial space (K), the transfer constant from the interstitial space to the blood plasma (kep), and the plasmatic volume fraction (Vp). RESULTS: Patients with systemic metastases had a significantly lower kep compared to those with local disease (0.45 vs. 0.99 min, P = 0.011). Metastatic burden correlated positively with K and standardized uptake value (SUV), and negatively with kep. Ki67 positive tumors had a significantly greater K compared to Ki67 negative tumors (0.29 vs. 0.45 min, P = 0.03). A negative correlation was found between metabolic tumor volume and transfer constant (K or Kep). CONCLUSION: These preliminary results suggest that MR pharmacokinetic parameters and FDG-PET may aid in the assessment of tumor aggressiveness and metastatic potential. Future studies are warranted with a larger cohort to further assess the role of pharmacokinetic modeling in simultaneous PET/MRI imaging.

OBJECTIVE: This article explores recent developments in PET and MRI, separately or combined, for assessing metastatic lymph nodes in patients with head and neck cancer. CONCLUSION: The synergistic role of PET and MRI for imaging metastatic lymph nodes has not been fully explored. To facilitate the understanding of the areas that need further investigation, we discuss potential mechanisms and evidence reported so far, as well as future directions and challenges for continued development and clinical research.

PURPOSE: To examine heterogeneous breast cancer through intravoxel incoherent motion (IVIM) histogram analysis. MATERIALS AND METHODS: This HIPAA-compliant, IRB-approved retrospective study included 62 patients (age 48.44 +/- 11.14 years, 50 malignant lesions and 12 benign) who underwent contrast-enhanced 3 T breast MRI and diffusion-weighted imaging. Apparent diffusion coefficient (ADC) and IVIM biomarkers of tissue diffusivity (Dt), perfusion fraction (fp), and pseudo-diffusivity (Dp) were calculated using voxel-based analysis for the whole lesion volume. Histogram analysis was performed to quantify tumour heterogeneity. Comparisons were made using Mann-Whitney tests between benign/malignant status, histological subtype, and molecular prognostic factor status while Spearman's rank correlation was used to characterize the association between imaging biomarkers and prognostic factor expression. RESULTS: The average values of the ADC and IVIM biomarkers, Dt and fp, showed significant differences between benign and malignant lesions. Additional significant differences were found in the histogram parameters among tumour subtypes and molecular prognostic factor status. IVIM histogram metrics, particularly fp and Dp, showed significant correlation with hormonal factor expression. CONCLUSION: Advanced diffusion imaging biomarkers show relationships with molecular prognostic factors and breast cancer malignancy. This analysis reveals novel diagnostic metrics that may explain some of the observed variability in treatment response among breast cancer patients. KEY POINTS: * Novel IVIM biomarkers characterize heterogeneous breast cancer. * Histogram analysis enables quantification of tumour heterogeneity. * IVIM biomarkers show relationships with breast cancer malignancy and molecular prognostic factors.

OBJECTIVES: To evaluate the associations between intravoxel incoherent motion (IVIM)-derived parameters and histopathological features and subtypes of breast cancer. METHODS: Preoperative magnetic resonance imaging from 275 patients with unilateral breast cancer was analyzed. The apparent diffusion coefficient (ADC) and IVIM parameters (Dt, tissue diffusion coefficient; fp, perfusion fraction; and Dp, pseudo-diffusion coefficient) were obtained from cancer and normal tissue using diffusion weighted imaging with b values of 0, 30, 70, 100, 150, 200, 300, 400, 500, and 800 s/. We then compared the IVIM parameters of tumors with different histopathological features and subtypes. RESULTS: ADC and Dt were lower and fp was higher in cancers than in normal tissues (p<0.001). Dt was lower in high Ki-67 cancer than in low Ki-67 cancer (p =0.019), whereas ADC showed no significant difference (p =0.309). Luminal B (HER2 negative) cancer showed lower ADC (p =0.003) and Dt (p =0.001) than other types. CONCLUSION: We found low tissue diffusivity in high Ki-67 cancer and luminal B (HER2 negative) cancer using IVIM imaging. Advances in Knowledge: Low tissue diffusivity is more clearly shown in high Ki-67 tumors and luminal B (HER2 negative) tumors with the IVIM model.

PURPOSE: To disentangle the free diffusivity (D0 ) and cellular membrane restrictions, by means of their surface-to-volume ratio (S/V), using the frequency-dependence of the diffusion coefficient D(omega), measured in brain tumors in the short diffusion-time regime using oscillating gradients (OGSE). METHODS: In vivo and ex vivo OGSE experiments were performed on mice bearing the GL261 murine glioma model (n = 10) to identify the relevant time/frequency (t/omega) domain where D(omega) linearly decreases with omega-1/2 . Parametric maps (S/V, D0 ) are compared with conventional DWI metrics. The impact of frequency range and temperature (20 degrees C versus 37 degrees C) on S/V and D0 is investigated ex vivo. RESULTS: The validity of the short diffusion-time regime is demonstrated in vivo and ex vivo. Ex vivo measurements confirm that the purely geometric restrictions embodied in S/V are independent from temperature and frequency range, while the temperature dependence of the free diffusivity D0 is similar to that of pure water. CONCLUSION: Our results suggest that D(omega) in the short diffusion-time regime can be used to uncouple the purely geometric restriction effect, such as S/V, from the intrinsic medium diffusivity properties, and provides a nonempirical and objective way to interpret frequency/time-dependent diffusion changes in tumors in terms of objective biophysical tissue parameters. Magn Reson Med, 2015. (c) 2015 Wiley Periodicals, Inc.