Effective delivery of therapeutic drug to the core of a tumor is often impeded by physiological barriers, such as interstitial fluid pressure (IFP). There are a number of therapies to lower IFP and induce tumor vascular normalization. However, lack of a non-invasive means to measure IFP hinders utilization of such a window of opportunity for maximizing 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 with diffusion weighted magnetic resonance 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 median apparent diffusion coefficient from the monoexponential model (r = 0.11, p = 0.78) or median tissue diffusivity from the biexponential model (r = 0.30, p = 0.44). On the other hand, IFP was correlated with the median pseudo-diffusivity (Dp) of apparent vascular voxels (r = 0.76, p = 0.02) and with the median product of perfusion-fraction and pseudo-diffusivity (fp·Dp) 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 using IVIM-DWI metrics as noninvasive biomarkers for tumor IFP.

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. Diffusionweighted 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 67:1710-1720,

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 1000 s/mm2) in addition to diagnostic MRI, were included. Patients with less than 0.8 cm 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.

HighlightsIntravoxel incoherent motion may predict response to breast neoadjuvant treatment.Histogram analysis amplifies IVIM by quantifying spatial heterogeneity.Pseudodiffusvity (Dp) showed the highest potential for response prediction.