Assessment of Hypoxia in Breast Cancer: Emerging Functional MR Imaging and Spectroscopy Techniques and Clinical Applications.

Breast cancer is one of the most prevalent forms of cancer affecting women worldwide. Hypoxia, a condition characterized by insufficient oxygen supply in tumor tissues, is closely associated with tumor aggressiveness, resistance to therapy, and poor clinical outcomes. Accurate assessment of tumor hypoxia can guide treatment decisions, predict therapy response, and contribute to the development of targeted therapeutic interventions. Over the years, functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS) techniques have emerged as promising noninvasive imaging options for evaluating hypoxia in cancer. Such techniques include blood oxygen level-dependent (BOLD) MRI, oxygen-enhanced MRI (OE) MRI, chemical exchange saturation transfer (CEST) MRI, and proton MRS (1H-MRS). These may help overcome the limitations of the routinely used dynamic contrast-enhanced (DCE) MRI and diffusion-weighted imaging (DWI) techniques, contributing to better diagnosis and understanding of the biological features of breast cancer. This review aims to provide a comprehensive overview of the emerging functional MRI and MRS techniques for assessing hypoxia in breast cancer, along with their evolving clinical applications. The integration of these techniques in clinical practice holds promising implications for breast cancer management. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 1.

Spatial profiling of in vivo diffusion-weighted MRI parameters in the healthy human kidney.

OBJECTIVE: Diffusion-weighted MRI is a technique that can infer microstructural and microcirculatory features from biological tissue, with particular application to renal tissue. There is extensive literature on diffusion tensor imaging (DTI) of anisotropy in the renal medulla, intravoxel incoherent motion (IVIM) measurements separating microstructural from microcirculation effects, and combinations of the two. However, interpretation of these features and adaptation of more specific models remains an ongoing challenge. One input to this process is a whole organ distillation of corticomedullary contrast of diffusion metrics, as has been explored for other renal biomarkers. MATERIALS AND METHODS: In this work, we probe the spatial dependence of diffusion MRI metrics with concentrically layered segmentation in 11 healthy kidneys at 3 T. The metrics include those from DTI, IVIM, a combined approach titled "REnal Flow and Microstructure AnisotroPy (REFMAP)", and a multiply encoded model titled "FC-IVIM" providing estimates of fluid velocity and branching length. RESULTS: Fractional anisotropy decreased from the inner kidney to the outer kidney with the strongest layer correlation in both parenchyma (including cortex and medulla) and medulla with Spearman correlation coefficients and p-values (r, p) of (0.42, <0.001) and (0.37, <0.001), respectively. Also, dynamic parameters derived from the three models significantly decreased with a high correlation from the inner to the outer parenchyma or medulla with (r, p) ranges of (0.46-0.55, <0.001). CONCLUSIONS: These spatial trends might find implications for indirect assessments of kidney physiology and microstructure using diffusion MRI.

Cardiac Phase and Flow Compensation Effects on REnal Flow and Microstructure AnisotroPy MRI in Healthy Human Kidney.

BACKGROUND: Renal diffusion-weighted imaging (DWI) involves microstructure and microcirculation, quantified with diffusion tensor imaging (DTI), intravoxel incoherent motion (IVIM), and hybrid models. A better understanding of their contrast may increase specificity. PURPOSE: To measure modulation of DWI with cardiac phase and flow-compensated (FC) diffusion gradient waveforms. STUDY TYPE: Prospective. POPULATION: Six healthy volunteers (ages: 22-48 years, five females), water phantom. FIELD STRENGTH/SEQUENCE: 3-T, prototype DWI sequence with 2D echo-planar imaging, and bipolar (BP) or FC gradients. 2D Half-Fourier Single-shot Turbo-spin-Echo (HASTE). Multiple-phase 2D spoiled gradient-echo phase contrast (PC) MRI. ASSESSMENT: BP and FC water signal decays were qualitatively compared. Renal arteries and velocities were visualized on PC-MRI. Systolic (peak velocity), diastolic (end stable velocity), and pre-systolic (before peak velocity) phases were identified. Following mutual information-based retrospective self-registration of DWI within each kidney, and Marchenko-Pastur Principal Component Analysis (MPPCA) denoising, combined IVIM-DTI analysis estimated mean diffusivity (MD), fractional anisotropy (FA), and eigenvalues (λi) from tissue diffusivity (Dt ), perfusion fraction (fp ), and pseudodiffusivity (Dp , Dp,axial , Dp,radial ), for each tissue (cortex/medulla, segmented on b0/FA respectively), phase, and waveform (BP, FC). Monte Carlo water diffusion simulations aided data interpretation. STATISTICAL TESTS: Mixed model regression probed differences between tissue types and pulse sequences. Univariate general linear model analysis probed variations among cardiac phases. Spearman correlations were measured between diffusion metrics and renal artery velocities. Statistical significance level was set at P < 0.05. RESULTS: Water BP and FC signal decays showed no differences. Significant pulse sequence dependence occurred for λ1 , λ3 , FA, Dp , fp , Dp,axial , Dp,radial in cortex and medulla, and medullary λ2 . Significant cortex/medulla differences occurred with BP for all metrics except MD (systole [P = 0.224]; diastole [P = 0.556]). Significant phase dependence occurred for Dp , Dp,axial , Dp,radial for BP and medullary λ1 , λ2 , λ3 , MD for FC. FA correlated significantly with velocity. Monte Carlo simulations indicated medullary measurements were consistent with a 34 µm tubule diameter. DATA CONCLUSION: Cardiac gating and flow compensation modulate of measurements of renal diffusion. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY STAGE: 2.

Multisite MRI Intravoxel Incoherent Motion Repeatability and Reproducibility across 3 T Scanners in a Breast Diffusion Phantom: A BReast Intravoxel Incoherent Motion Multisite (BRIMM) Study.

BACKGROUND: Monoexponential apparent diffusion coefficient (ADC) and biexponential intravoxel incoherent motion (IVIM) analysis of diffusion-weighted imaging is helpful in the characterization of breast tumors. However, repeatability/reproducibility studies across scanners and across sites are scarce. PURPOSE: To evaluate the repeatability and reproducibility of ADC and IVIM parameters (tissue diffusivity (Dt ), perfusion fraction (Fp ) and pseudo-diffusion (Dp )) within and across sites employing MRI scanners from different vendors utilizing 16-channel breast array coils in a breast diffusion phantom. STUDY TYPE: Phantom repeatability. PHANTOM: A breast phantom containing tubes of different polyvinylpyrrolidone (PVP) concentrations, water, fat, and sponge flow chambers, together with an MR-compatible liquid crystal (LC) thermometer. FIELD STRENGTH/SEQUENCE: Bipolar gradient twice-refocused spin echo sequence and monopolar gradient single spin echo sequence at 3 T. ASSESSMENT: Studies were performed twice in each of two scanners, located at different sites, on each of 2 days, resulting in four studies per scanner. ADCs of the PVP and water were normalized to the vendor-provided calibrated values at the temperature indicated by the LC thermometer for repeatability/reproducibility comparisons. STATISTICAL TESTS: ADC and IVIM repeatability and reproducibility within and across sites were estimated via the within-system coefficient of variation (wCV). Pearson correlation coefficient (r) was also computed between IVIM metrics and flow speed. A P value <0.05 was considered statistically significant. RESULTS: ADC and Dt demonstrated excellent repeatability (<2%; <3%, respectively) and reproducibility (both <5%) at the two sites. Fp and Dp exhibited good repeatability (mean of two sites 3.67% and 5.59%, respectively) and moderate reproducibility (mean of two sites 15.96% and 13.3%, respectively). The mean intersite reproducibility (%) of Fp /Dp /Dt was 50.96/13.68/5.59, respectively. Fp and Dt demonstrated high correlations with flow speed while Dp showed lower correlations. Fp correlations with flow speed were significant at both sites. DATA CONCLUSION: IVIM reproducibility results were promising and similar to ADC, particularly for Dt . The results were reproducible within both sites, and a progressive trend toward reproducibility across sites except for Fp . LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Characterization of motion dependent magnetic field inhomogeneity for DWI in the kidneys.

PURPOSE: Diffusion-weighted imaging (DWI) of the abdomen has increased dramatically for both research and clinical purposes. Motion and static field inhomogeneity related challenges limit image quality of abdominopelvic imaging with the most conventional echo-planar imaging (EPI) pulse sequence. While reversed phase encoded imaging is increasingly used to facilitate distortion correction, it typically assumes one motion independent magnetic field distribution. In this study, we describe a more generalized workflow for the case of kidney DWI in which the field inhomogeneity at multiple respiratory phases is mapped and used to correct all images in a multi-contrast DWI series. METHODS: In this HIPAA-compliant and IRB-approved prospective study, 8 volunteers (6 M, ages 28-51) had abdominal imaging performed in a 3 T MRI system (MAGNETOM Prisma; Siemens Healthcare, Erlangen, Germany) with ECG gating. Coronal oblique T2-weighted HASTE images were collected for anatomical reference. Sagittal phase-contrast (PC) MRI images through the left renal artery were collected to determine systolic and diastolic phases. Cardiac triggered oblique coronal DWI were collected at 10 b-values between 0 and 800 s/mm2 and 12 directions. DWI series were distortion corrected using field maps generated by forward and reversed phase encoded b = 0 images collected over the full respiratory cycle and matched by respiratory phase. Morphologic accuracy, intraseries spatial variability, and diffusion tensor imaging (DTI) metrics mean diffusivity (MD) and fractional anisotropy (FA) were compared for results generated with no distortion correction, correction with only one respiratory bin, and correction with multiple respiratory bins across the breathing cycle. RESULTS: Computed field maps showed significant variation in static field with kidney laterality, region, and respiratory phase. Distortion corrected images showed significantly better registration to morphologic images than uncorrected images; for the left kidney, the multiple bin correction outperformed one bin correction. Line profile analysis showed significantly reduced spatial variation with multiple bins than one bin correction. DTI metrics were mostly similar between correction methods, with some differences observed in MD between uncorrected and corrected datasets. CONCLUSIONS: Our results indicate improved morphology of kidney DWI and derived parametric maps as well as reduced variability over the full image series using the motion-resolved distortion correction. This work highlights some morphologic and quantitative metric improvements can be obtained for kidney DWI when distortion correction is performed in a respiratory-resolved manner.