Apparent diffusion coefficient in estrogen receptor-positive and lymph node-negative invasive breast cancers at 3.0T DW-MRI: A potential predictor for an oncotype Dx test recurrence score.

PURPOSE: To measure the apparent diffusion coefficient (ADC) values in estrogen receptor-positive (ER+) and axillary lymph node-negative (LN-) invasive breast cancer and investigate the correlation of ADC with Oncotype Dx test recurrence scores (ODxRS). MATERIALS AND METHODS: This was a Health Insurance Portability and Accountability Act (HIPAA)-compliant single-site retrospective study. Patients underwent preoperative 3.0T MRI scans with additional diffusion-weighted imaging sequential scans (b = 0, 600 and b = 0, 1000 s/mm2 ) from January 2011 to 2013. The study population included 31 ER+/LN- invasive breast cancers, which underwent ODxRS genomic testing. ADC600 and ADC1000 parametric maps were generated, and ADC values were calculated from a user-drawn region of interest. ODxRS predicts 10-year recurrence risk in individual patients: low (RS <18), intermediate (RS: 18-30), or high (RS >30). All breast lesions, including subgroups of invasive ductal carcinoma (IDC) lesions and mass-only lesions were dichotomized by RS scores, low-risk versus intermediate/high-risk, and statistical analysis was performed using Mann-Whitney's test (statistical significance at P < 0.05) and receiver operating characteristic (ROC) curves. Multivariate analysis was also performed. RESULTS: Invasive breast cancers, when scored as low-risk by ODxRS, had significantly higher ADC values compared with intermediate/high-risk lesions for both ADC600 (P = 0.007) and ADC1000 (P = 0.008) mean values. This was true both when analyzing only mass-lesions (P = 0.03 and 0.01) or only IDCs (P = 0.001 and 0.009). CONCLUSION: Preliminary findings suggest that lesion ADC values correlate with recurrence risk likelihood stratified using ODxRS. Hence, ADC is a potential surrogate biomarker for tumor aggressiveness. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2018;47:401-409.

Intravoxel incoherent motion (IVIM) histogram biomarkers for prediction of neoadjuvant treatment response in breast cancer patients.

OBJECTIVE: To examine the prognostic capabilities of intravoxel incoherent motion (IVIM) metrics and their ability to predict response to neoadjuvant treatment (NAT). Additionally, to observe changes in IVIM metrics between pre- and post-treatment MRI. METHODS: This IRB-approved, HIPAA-compliant retrospective study observed 31 breast cancer patients (32 lesions). Patients underwent standard bilateral breast MRI along with diffusion-weighted imaging before and after NAT. Six patients underwent an additional IVIM-MRI scan 12-14 weeks after initial scan and 2 cycles of treatment. In addition to apparent diffusion coefficients (ADC) from monoexponential decay, IVIM mean values (tissue diffusivity Dt, perfusion fraction fp, and pseudodiffusivity Dp) and histogram metrics were derived using a biexponential model. An additional filter identified voxels of highly vascular tumor tissue (VTT), excluding necrotic or normal tissue. Clinical data include histology of biopsy and clinical response to treatment through RECIST assessment. Comparisons of treatment response were made using Wilcoxon rank-sum tests. RESULTS: Average, kurtosis, and skewness of pseudodiffusion Dp significantly differentiated RECIST responders from nonresponders. ADC and Dt values generally increased (∼70%) and VTT% values generally decreased (∼20%) post-treatment. CONCLUSION: Dp metrics showed prognostic capabilities; slow and heterogeneous pseudodiffusion offer poor prognosis. Baseline ADC/Dt parameters were not significant predictors of response. This work suggests that IVIM mean values and heterogeneity metrics may have prognostic value in the setting of breast cancer NAT.

Voxelwise analysis of simultaneously acquired and spatially correlated 18 F-fluorodeoxyglucose (FDG)-PET and intravoxel incoherent motion metrics in breast cancer.

PURPOSE: Diffusion-weighted imaging (DWI) and 18 F-fluorodeoxyglucose-positron emission tomography (18 F-FDG-PET) independently correlate with malignancy in breast cancer, but the relationship between their structural and metabolic metrics is not completely understood. This study spatially correlates diffusion, perfusion, and glucose avidity in breast cancer with simultaneous PET/MR imaging and compares correlations with clinical prognostics. METHODS: In this Health Insurance Portability and Accountability Act-compliant prospective study, with written informed consent and approval of the institutional review board and using simultaneously acquired FDG-PET and DWI, tissue diffusion (Dt ), and perfusion fraction (fp ) from intravoxel incoherent motion (IVIM) analysis were registered to FDG-PET within 14 locally advanced breast cancers. Lesions were analyzed using 2D histograms and correlation coefficients between Dt , fp , and standardized uptake value (SUV). Correlations were compared with prognostics from biopsy, metastatic burden from whole-body PET, and treatment history. RESULTS: SUV||Dt correlation coefficient significantly distinguished treated (0.11 ± 0.24) from nontreated (-0.33 ± 0.26) patients (P = 0.005). SUV||fp correlations were on average negative for the whole cohort (-0.17 ± 0.13). CONCLUSION: Simultaneously acquired and registered FDG-PET/DWI allowed quantifiable descriptions of breast cancer microenvironments that may provide a framework for monitoring and predicting response to treatment. Magn Reson Med 78:1147-1156, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Stimulated echo diffusion tensor imaging (STEAM-DTI) with varying diffusion times as a probe of breast tissue.

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 µm, 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. LEVEL OF EVIDENCE: 2 J. Magn. Reson. Imaging 2017;45:84-93.

Quantitative apparent diffusion coefficient measurement obtained by 3.0Tesla MRI as a potential noninvasive marker of tumor aggressiveness in breast cancer.

PURPOSE: To assess the association between apparent diffusion coefficient (ADC), and histological prognostic parameters in malignant breast lesions. The ability of ADC to identify lesions with the presence of Lymphovascular invasion (LVI) in breast carcinoma was also examined. MATERIALS AND METHODS: This HIPAA-compliant retrospective study consisted of 212 consecutive patients with known cancers who underwent 3.0T MRI between January 2011 and 2013. In this study, a total of 126 malignant lesions in 114 women, who had undergone DWI (b-values of 0 and 1000s/mm(2)) in addition to diagnostic MRI, were included. Patients with less than 0.8cm lesions, or those who underwent neoadjuvant chemotherapy or suboptimal DW images were excluded. Classical prognostic factors [lesion size, histopathological type and grade, lymph node (LN) status and lymphovascular invasion (LVI)], molecular prognostic markers [estrogen receptor (ER), progesterone receptor (PR) and human epidermal grow factor receptor 2 (HER2)] were reviewed and recorded. A region of interest (ROI) was drawn within the lesions to measure ADC values. Statistical analyses were performed by the Wilcoxon rank sum test (statistical significance at P<0.05). Adjusted p values from multiple comparison analysis were also calculated. RESULTS: This study demonstrates an inverse correlation between ADC and LVI in malignant lesions and the ability of ADC to identify aggressiveness in lesions with positive LVI. Tumor size, grade, ER, PR, HER2 and lymph node status did not impact tumor ADC value. However, tumors with LVI showed significantly lower ADC values when compared to tumors without LVI, regardless of the enhancement type, histological grade, histological type, and LN status. CONCLUSION: Our study shows that ADC could be a potential clinical adjunct in the evaluation of prognostic factors related to malignant lesion aggressiveness such as LVI.

Dynamic diffusion-tensor measurements in muscle tissue using the single-line multiple-echo diffusion-tensor acquisition technique at 3T.

When diffusion biomarkers display transient changes, i.e. in muscle following exercise, traditional diffusion-tensor imaging (DTI) methods lack the temporal resolution to resolve the dynamics. This article presents an MRI method for dynamic diffusion-tensor acquisitions on a clinical 3T scanner. This method, the Single-Line Multiple-Echo Diffusion-Tensor Acquisition Technique (SL-MEDITATE), achieves a high temporal resolution (4 s) by rapid diffusion encoding through the acquisition of multiple echoes with unique diffusion sensitization and limiting the readout to a single line volume. The method is demonstrated in a rotating anisotropic phantom, a flow phantom with adjustable flow speed and in vivo skeletal calf muscle of healthy volunteers following a plantar flexion exercise. The rotating and flow-varying phantom experiments show that SL-MEDITATE correctly identifies the rotation of the first diffusion eigenvector and the changes in diffusion-tensor parameter magnitudes, respectively. Immediately following exercise, the in vivo mean diffusivity (MD) time courses show, before the well-known increase, an initial decrease that is not typically observed in traditional DTI. In conclusion, SL-MEDITATE can be used to capture transient changes in tissue anisotropy in a single line. Future progress might allow for dynamic DTI when combined with appropriate k-space trajectories and compressed sensing reconstruction.

A method for safety testing of radiofrequency/microwave-emitting devices using MRI.

PURPOSE: Strict regulations are imposed on the amount of radiofrequency (RF) energy that devices can emit to prevent excessive deposition of RF energy into the body. In this study, we investigated the application of MR temperature mapping and 10-g average specific absorption rate (SAR) computation for safety evaluation of RF-emitting devices. METHODS: Quantification of the RF power deposition was shown for an MRI-compatible dipole antenna and a non-MRI-compatible mobile phone via phantom temperature change measurements. Validation of the MR temperature mapping method was demonstrated by comparison with physical temperature measurements and electromagnetic field simulations. MR temperature measurements alongside physical property measurements were used to reconstruct 10-g average SAR. RESULTS: The maximum temperature change for a dipole antenna and the maximum 10-g average SAR were 1.83°C and 12.4 W/kg, respectively, for simulations and 1.73°C and 11.9 W/kg, respectively, for experiments. The difference between MR and probe thermometry was <0.15°C. The maximum temperature change and the maximum 10-g average SAR for a cell phone radiating at maximum output for 15 min was 1.7°C and 0.54 W/kg, respectively. CONCLUSION: Information acquired using MR temperature mapping and thermal property measurements can assess RF/microwave safety with high resolution and fidelity.

A versatile flow phantom for intravoxel incoherent motion MRI.

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.

Interstitial fluid pressure correlates with intravoxel incoherent motion imaging metrics in a mouse mammary carcinoma model.

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.