Following its success in early detection of cerebral ischemia, diffusion-weighted imaging (DWI) has been increasingly used in cancer diagnosis and treatment evaluation. These applications are propelled by the rapid development of novel diffusion models to extract biologically valuable information from diffusion-weighted MR signals, and significant advances in MR hardware that has enabled image acquisition with high b-values. This article reviews recent technical developments and clinical applications in cancer imaging using DWI, with a special emphasis on high b-value diffusion models. The article is organized in four sections. First, we provide an overview of diffusion models that are relevant to cancer imaging. The model parameters are discussed in relation to three tissue properties-cellularity, vascularity, and microstructures. An emphasis is placed on characterization of microstructural heterogeneity, given its novelty and close relevance to cancer. Second, we illustrate diffusion MR clinical applications in each of the following three categories: 1) cancer detection and diagnosis; 2) cancer grading, staging, and classification; and 3) cancer treatment response prediction and evaluation. Third, we discuss several practical issues, including selection of image acquisition parameters, reproducibility and reliability, motion management, image distortion, etc., that are commonly encountered when applying DWI to cancer in clinical settings. Lastly, we highlight a few ongoing challenges and provide some possible future directions, particularly in the area of establishing standards via well-organized multicenter clinical trials to accelerate clinical translation of advanced DWI techniques to improving cancer care on a large scale. Level of Evidence: 5 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:23-40.

/pdf/diffusion-mri-of-cancer-from-low-to-high-b-values-1v7r36zdyo.pdf

Diffusion MRI of cancer: From low to high b-values.

Recent developments in MR hardware and software have allowed a surge of interest in intravoxel incoherent motion (IVIM) MRI in oncology. Beyond diffusion-weighted imaging (and the standard apparent diffusion coefficient mapping most commonly used clinically), IVIM provides information on tissue microcirculation without the need for contrast agents. In oncology, perfusion-driven IVIM MRI has already shown its potential for the differential diagnosis of malignant and benign tumors, as well as for detecting prognostic biomarkers and treatment monitoring. Current developments in IVIM data processing, and its use as a method of scanning patients who cannot receive contrast agents, are expected to increase further utilization. This paper reviews the current applications, challenges, and future trends of perfusion-driven IVIM in oncology.

Perfusion-driven Intravoxel Incoherent Motion (IVIM) MRI in Oncology: Applications, Challenges, and Future Trends.

The diagnostic performance of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) in the differential diagnosis of pulmonary tumors remained debatable among published studies. This study aimed to pool and summary the relevant results to provide more robust evidence in this issue using a meta-analysis method. The researches regarding the differential diagnosis of lung lesions using IVIM-DWI were systemically searched in Pubmed, Embase, Web of science and Wangfang database without time limitation. Review Manager 5.3 was used to calculate the standardized mean difference (SMD) and 95% confidence intervals of apparent diffusion coefficient (ADC), tissue diffusivity (D), pseudo-diffusivity (D*), and perfusion fraction (f). Stata 12.0 was used to pool the sensitivity, specificity, and area under the curve (AUC), as well as publication bias and heterogeneity. Fagan’s nomogram was used to predict the post-test probabilities. Eleven studies with 481 malignant and 258 benign lung lesions were included. Most include studies showed a low to unclear risk of bias and low concerns regarding applicability. Lung cancer demonstrated a significant lower ADC (SMD = -1.17, P < 0.001), D (SMD = -1.02, P < 0.001) and f values (SMD = -0.43, P = 0.005) than benign lesions, except D* value (SMD = 0.01, P = 0.96). D value demonstrated the best diagnostic performance (sensitivity = 89%, specificity = 71%, AUC = 0.90) and highest post-test probability (57, 57, 43 and 43% for D, ADC, f and D* values) in the differential diagnosis of lung tumors, followed by ADC (sensitivity = 85%, specificity = 72%, AUC = 0.86), f (sensitivity = 71%, specificity = 61%, AUC = 0.71) and D* values (sensitivity = 70%, specificity = 60%, AUC = 0.66). IVIM-DWI parameters show potentially strong diagnostic capabilities in the differential diagnosis of lung tumors based on the tumor cellularity and perfusion characteristics, and D value demonstrated better diagnostic performance compared to mono-exponential ADC.

/pdf/differentiating-the-lung-lesions-using-intravoxel-incoherent-4ulpa0z37n.pdf

Differentiating the lung lesions using Intravoxel incoherent motion diffusion-weighted imaging: a meta-analysis

Diagnosis of solitary pulmonary lesions with intravoxel incoherent motion diffusion-weighted MRI and semi-quantitative dynamic contrast-enhanced MRI.

Objective The aim of the study was to compare intravoxel incoherent motion diffusion-weighted imaging (DWI) for evaluating lung cancer using single-shot turbo spin-echo (TSE) and single-shot echo-planar imaging (EPI) in a 3T MR system. Methods Both single-shot TSE-DWI and single-shot EPI-DWI were scanned twice respectively for 15 patients with lung cancer. Distortion ratio, signal-to-noise ratio, and contrast-to-noise ratio were compared between the 2 techniques. The Bland-Altman analysis was performed to analyze reproducibility between the parameters of TSE-DWI and EPI-DWI. Short-term test-retest repeatability, as well as interobserver agreement, was evaluated using the coefficient of variation (CV) and the intraclass correlation coefficient (ICC). Result Turbo spin-echo DWI has lower signal-to-noise ratio and similar contrast-to-noise ratio compared with EPI-DWI. Distortion ratio of TSE-DWI was significantly smaller than that of EPI-DWI. The apparent diffusion coefficient (ADC) and true diffusivity (D) of TSE-DWI showed higher values than those of EPI-DWI. The Bland-Altman analysis showed unacceptable limits of agreement between these 2 sequences. Test-retest repeatability was good for ADC and D of EPI-DWI (CV, 14.11%-16.60% and 17.08%-19.53%) and excellent for ADC and D of TSE-DWI (CV, 4.8%-6.19% and 6.05%-8.71%), but relatively poor for perfusion fraction (f) and pseudo-diffusion coefficient (D*) (CV, 25.95%-27.70% and 56.92%-71.84% for EPI, 23.67%-28.67% and 60.85%-70.17% for TSE). For interobserver agreement, both techniques were good to excellent in ADC and D (The lower limit of 95% confidence interval for ICC was almost all greater than 0.75), whereas D* and f had higher interobserver variabilities with D* of TSE-DWI showing poorest reproducibility (ICC, -0.27 to 0.12). Conclusions Lung DWI or IVIM using TSE could provide distortion-free images and improve the test-retest robustness of ADC and D as compared with EPI-DWI; however, it might exert a negative effect on perfusion parameter D*.

Intravoxel Incoherent Motion Diffusion-Weighted Imaging of Lung Cancer: Comparison Between Turbo Spin-Echo and Echo-Planar Imaging.

Purpose To prospectively evaluate the short-term reproducibility of intravoxel incoherent motion (IVIM) parameters and apparent diffusion coefficient (ADC) in lung cancer patients. Materials and methods In all, 50 patients (50 lesions) underwent free-breathing diffusion-weighted imaging (DWI) (b = 0, 300, 800 s/mm2 ) and IVIM (10 b-values, 0-1000 s/mm2 ) scans twice (0.5-1-hour interval) at 3T. Regions of interests (ROIs) were drawn on ADC maps and IVIM images to derive the mean ADC value and IVIM parameters D, D*, and f. Intra- and interobserver, test-retest reproducibility were assessed with intraclass correlation coefficients (ICCs), within coefficient-of-variations (WCVs), and Bland-Altman analysis. The effects of type, size, and location of lung lesions were compared with WCVs. Results D and ADC showed good intraobserver reproducibility and interobserver agreement, while D* and f showed relatively larger variability (WCV 20.89-34.97%). The test-retest reproducibility of D and ADC were good (ICC 0.763-0.837; WCV 11.12-12.55%), while those of D* and f were relatively poor (ICC 0.604-0.842; WCV 36.54-72.62%). D and ADC had decreased reproducibility for lesions 2 cm (WCV 42.64%). D* had even worse reproducibility in peripheral lung cancers (WCV 84.11%) and lesions in the lower lung zones (WCV 80.84%). Conclusion If the change in ADC, D, D*, and f values is less than ∼31%, 34%, 170%, and 130%, respectively, it may be caused by measurement error. The type, size, and location of lung lesions have an effect on measurement errors. Level of evidence 1 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2018;47:1003-1012.

Lung Cancer: Short‐Term Reproducibility of Intravoxel Incoherent Motion Parameters and Apparent Diffusion Coefficient at 3T

Objective
To investigate the ADC value and intravoxel incoherent motion (IVIM) parameters to predict the early response to chemotherapy in patients with locally advanced non-small cell lung cancer (NSCLC). 


Methods
Twenty-six patients with pathologically confirmed NSCLC in our hospital from June 2015 to January 2017 were prospectively studied. MR routine scan, DWI and IVIM scans were performed before and at the end of the first cycle of chemotherapy. The ADC value, pure diffusion parameter (D), perfusion parameter (D*) and perfusion fraction (f) before and after chemotherapy were recorded respectively, and the maximum diameter of tumor (MDMRI) was measured on T2WI. The effective group and the ineffective group were divided according to RECIST 1.1. Intra-and interobserver reproducibility were assessed with intraclass correlation coefficient (ICC). The differences of the parameters and their change rate were compared pre- and posttreatment, in the effective and the ineffective groups by using t test. Receiver operating characteristic (ROC) curves were generated to explore the optimal parameters and thresholds for early prediction of the efficacy of chemotherapy. Z test was used to compare the differences in the areas under the ROC curves. 


Results
The repeatability of D* was relatively poor (ICC 0.507-0.716). The ADC and D values of the effective group before chemotherapy were (1.28±0.21)×10-3 and (1.05±0.14)×10-3mm2/s, respectively, and those of the ineffective group were (1.55±0.25)×10-3 and (1.29±0.18)×10-3mm2/s, respectively. The differences between two groups were statistically significant (t=-2.989, - 3.755, respectively, P all 0.05, respectively). The difference of f was statistically significant (t=-2.731, P 0.05). 


Conclusion
The ADC value, D value before chemotherapy and the early change rate after chemotherapy can better predict the early response of chemotherapy in NSCLC patients.


Key words: 
Carcinoma, non-small-cell lung; Magnetic resonance imaging; Treatment outcome

The value of diffusion-weighted imaging based on monoexponential and biexponential model in predicting the response of chemotherapy in non-small cell lung cancer patients

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Lung Cancer: Short‐Term Reproducibility of Intravoxel Incoherent Motion Parameters and Apparent Diffusion Coefficient at 3T

The value of diffusion-weighted imaging based on monoexponential and biexponential model in predicting the response of chemotherapy in non-small cell lung cancer patients