Intravoxel Incoherent Motion Diffusion-weighted MRI Research Articles

Intravoxel incoherent motion diffusion-weighted MRI assessing the effect of the vascular disrupting agent CA4P on VX2 liver tumors in rabbits.

This study aimed to assess the response of combretastatin-A4-phosphate (CA4P) in rabbit VX2 liver tumors using intravoxel incoherent motion diffusion-weighted MRI (IVIM DW-MRI). Forty rabbits with implanted VX2 liver tumors underwent baseline MRI and were then given 10 mg/kg CA4P (n=20) or saline (n=20). After 4 h, 10 rabbits from each group underwent an MRI examination and were then sacrificed. The remaining rabbits underwent MRI after 1, 3, and 7 days and were then sacrificed. Liver samples were processed for H&E and immunohistochemical staining. IVIM parameters (D, f, D*) were compared in the treatment and control groups, and the correlations of IVIM parameters with microvascular density (MVD) were determined. At 4 h, the two treatment groups had significantly different f and D* values (p<0.001), and these values were at their minimum in the treatment group. The treatment group had moderate correlations between MVD and f at 4 h (r=0.676, p=0.032) and 7 days (r=0.656, p=0.039) and with D* at 4 h (r=0.732, p=0.016) and 7 days (r=0.748, p=0.013), but no correlation was reported between MVD and f or D* in the control group (all P>0.05). IVIM DW-MRI is a sensitive imaging technique. It successfully evaluated the effect of CA4P on VX2 liver tumors in rabbits. The f and D* values correlated with MVD at 4 h and 7 days after using CA4P, indicating that these parameters have the potential to be used as indicators of tumor angiogenesis after treatment.

Intravoxel incoherent motion diffusion-weighted MRI for predicting the efficacy of high-intensity focused ultrasound ablation for uterine fibroids.

To evaluate the significance of magnetic resonance (MR) intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) quantitative parameters in predicting early efficacy of high-intensity focused ultrasound (HIFU) ablation of uterine fibroids before treatment. 64 patients with 89 uterine fibroids undergoing HIFU ablation (51 sufficient ablations and 38 insufficient ablations) were enrolled in the study and completed MR imaging and IVIM-DWI before treatment. The IVIM-DWI parameters, including D (diffusion coefficient), D* (pseudo-diffusion coefficient), f (perfusion fraction) and relative blood flow (rBF) were calculated. The logistic regression (LR) model was constructed to analyze the predictors of efficacy. The receiver operating characteristic (ROC) curve was drawn to assess the model's performance. A nomograph was constructed to visualize the model. The D value of the sufficient ablation group (931.0(851.5-987.4) × 10-6 mm2/s) was significantly lower than that of the insufficient ablation group (1052.7(1019.6-1158.7) × 10-6 mm2/s) (p<0.001). However, differences in D*, f, and rBF values between the groups were not significant (p>0.05). The LR model was constructed with D value, fibroid position, ventral skin distance, T2WI signal intensity, and contrast enhanced degree. The area under the ROC curve, specificity, and sensitivity of the model were 0.858 (95% confidence interval: 0.781, 0.935), 0.686, and 0.947. The nomogram and calibration curves confirmed that the model had excellent performance. The IVIM-DWI quantitative parameters can be used to predict early effects of HIFU ablation on uterine fibroids. A high D value before treatment may indicate that the treatment will be less effective in the early stages.

Intravoxel incoherent motion diffusion-weighted MRI of renal parenchyma and its clinical significance in patients with untreated acute leukemia: a pilot study.

To evaluate quantitative parameters derived from intravoxel incoherent motion diffusion-weighted MRI (IVIM) of renal parenchyma in patients with untreated acute leukemia (AL) and analyze its prognostic significance and probable pathological mechanism. From March 2019 to November 2021, 67 newly diagnosed AL patients and 67 healthy controls matched in age and sex were recruited. All participants underwent IVIM in the kidneys, and D, D*, f, standard ADC values were measured. The differences of all parameters between AL and controls were analyzed. The relationship between imaging parameters and estimated glomerular filtration rate (eGFR) was studied. Univariable and multivariable analyses were performed to investigate prognostic significance of possible indicators. The f and D value of renal medulla and D value of renal cortex in AL patients were lower than those in the healthy control group (t = -2.173, t = -3.463, t = -2.030, respectively, all P < 0.05). The cortical f, cortical standard ADC, medullary f, and medullary standard ADC were correlated with the eGFR (r = 0.524, r = 0.401, r = 0.415, r = 0.325, respectively, all P < 0.05) in patients with AL. A medullary f value ≤ 9.51% (hazard ratio: 0.282; 95% confidence interval: 0.110, 0.719; P = 0.008) was associated with overall survival in a multivariable analysis. The f and standard ADC values in renal parenchyma were the probable imaging markers of renal function in patients with newly diagnosed de novo AL. Lower renal medullary f value was a potential independent predictor for overall survival.

Phase I/II Study of LDE225 in Combination with Gemcitabine and Nab-Paclitaxel in Patients with Metastatic Pancreatic Cancer.

Simple SummaryOne of the reasons for treatment resistance of PDAC is the desmoplastic reaction initiating the production of large amounts of tumor stroma. LDE225 is a pharmacological Hedgehog signaling pathway inhibitor and is thought to specifically target tumor stroma. LDE225 in combination with gemcitabine and nab-paclitaxel was well-tolerated in patients with metastatic PDAC and has promising efficacy after prior treatment with FOLFIRINOX. Quantitative MRI suggested that LDE225 causes increased tumor diffusion and works particularly well in patients with poor baseline tumor perfusion. This suggests a clinical benefit of gemcitabine and nab-paclitaxel in combination with LDE225 in patients who received prior FOLFIRINOX. Future phase III clinical trials should confirm these results. Background: Desmoplasia is a central feature of the tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC). LDE225 is a pharmacological Hedgehog signaling pathway inhibitor and is thought to specifically target tumor stroma. We investigated the combined use of LDE225 and chemotherapy to treat PDAC patients. Methods: This was a multi-center, phase I/II study for patients with metastatic PDAC establishing the maximum tolerated dose of LDE225 co-administered with gemcitabine and nab-paclitaxel (phase I) and evaluating the efficacy and safety of the treatment combination after prior FOLFIRINOX treatment (phase II). Tumor microenvironment assessment was performed with quantitative MRI using intra-voxel incoherent motion diffusion weighted MRI (IVIM-DWI) and dynamic contrast-enhanced (DCE) MRI. Results: The MTD of LDE225 was 200 mg once daily co-administered with gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2. In phase II, six therapy-related grade 4 adverse events (AE) and three grade 5 were observed. In 24 patients, the target lesion response was evaluable. Three patients had partial response (13%), 14 patients showed stable disease (58%), and 7 patients had progressive disease (29%). Median overall survival (OS) was 6 months (IQR 3.9–8.1). Blood plasma fraction (DCE) and diffusion coefficient (IVIM-DWI) significantly increased during treatment. Baseline perfusion fraction could predict OS (>222 days) with 80% sensitivity and 85% specificity. Conclusion: LDE225 in combination with gemcitabine and nab-paclitaxel was well-tolerated in patients with metastatic PDAC and has promising efficacy after prior treatment with FOLFIRINOX. Quantitative MRI suggested that LDE225 causes increased tumor diffusion and works particularly well in patients with poor baseline tumor perfusion.

Simplified intravoxel incoherent motion diffusion-weighted MRI of liver lesions: feasibility of combined two-colour index maps

BackgroundTo evaluate the feasibility of two-colour index maps containing combined diffusion and perfusion information from simplified intravoxel incoherent motion (IVIM) for liver lesion malignancy assessment.MethodsDiffusion-weighted data from a respiratory-gated 1.5-T magnetic resonance sequence were analysed in 109 patients with liver lesions. With three b values (0, 50, 800 s/mm2) estimated diffusion coefficient D′, perfusion fraction f′, and apparent diffusion coefficient (ADC) maps were calculated and analysed for regions of interest (ROIs). D′ and f′ cutoff values were determined by differentiating haemangiomas from other lesions and focal nodular hyperplasias from other lesions, respectively. Combined IDf index maps were generated with a voxel value set to 100, if both D′ and f′ voxel values were lower than their cutoff values (1,529.4 × 10-6 mm2/s and 114.4 × 10-3, respectively), otherwise to 0. Moreover, IADC index maps were generated from ADC cutoff value (1,338.5 × 10-6 mm2/s) obtained by differentiating benign from malignant lesions. Discriminatory power was assessed for both IDf and IADC. Index maps were displayed as two-colour overlays to b-800 images and visually assessed within the translucent hyperintense areas.ResultsFor IDf, the same diagnostic accuracy was achieved as for the combined use of parameters D′ and f′ (93.6%). Compared to IADC, IDf showed a higher diagnostic accuracy. Visual judgment of IDf yielded an accuracy (95.4%) similar to that of quantitative analysis (93.6%).ConclusionVoxel-wise combined two-colour index maps IDf provide similar diagnostic accuracy as ROI-based combination of estimated IVIM parameters D′ and f′ and are suitable for visual assessment of liver lesion malignancy.

Phase I/II study of LDE225 in combination with gemcitabine and nab-paclitaxel in patients with metastatic pancreatic cancer.

e16239 Background: In pancreatic ductal adenocarcinoma (PDAC) desmoplasia is a central feature of the tumor microenvironment. By targeting both tumor cells and tumor stoma, treatment efficacy can be increased. LDE225 is a pharmacological Hedgehog signaling pathway inhibitor and is thought to specifically target tumor stroma. We investigated the combined use of LDE225 and chemotherapy in PDAC patients. Methods: The objective of phase I of the study was to established the maximum tolerated dose (MTD) of LDE225 co-administered with gemcitabine and nab-paclitaxel (ESMO 2017). The objective of phase II was to evaluate efficacy and safety of the treatment combination after prior fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX; ESMO 2019). Tumor response evaluation was performed using CT scan. Tumor microenvironment was assessed with functional MRI using intra-voxel incoherent motion diffusion weighted MRI (IVIM-DWI) and dynamic contrast enhanced (DCE) MRI. Also, the predictive value of IVIM-DWI and DCE MRI parameters on overall survival (OS) using ROC curves was determined. Results: The MTD of LDE225 was 200 mg once daily co-administered with gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2 on days 1, 8 and 15 of a 4-week cycle. We combined the outcomes of the five patients of phase I that received 200mg LDE225 and had prior treatment with FOLFIRINOX (n = 25 patients in total) in phase II. Most patients had WHO performance status of 0-1 (93%) and 57% were male. Patients were treated with a median number of two cycles (IQR 2-6). Six therapy related grade 4 adverse events (AE) were observed: sepsis (2), neutropenia (2), elevated gamma GT (1) and thromboembolic event (1), and three grade 5 (sepsis, pneumonia and progressive disease). Most common grade 3 therapy related AEs were neutropenia (37%) and diarrhea (14.8%). Patients discontinued treatment because of progressive disease (22), bacterial infection (1), sepsis (1) and diminished quality of life (1). In 24 patients target lesion response was evaluable. Three patients had partial response (13%), 14 patients showed stable disease (58%) and 7 patients had progressive disease (29%). The median OS was 6 months (IQR 3.9-8.1). Blood plasma fraction (DCE) and diffusion coefficient (IVIM-DWI) significantly increased during treatment. Baseline perfusion fraction can predict OS ( &gt; 222 days) with 80% sensitivity and 85% specificity. Conclusions: This study shows that LDE225 in combination with gemcitabine and nab-paclitaxel is well-tolerated in patients with metastatic PDAC and has promising efficacy after prior treatment with FOLFIRINOX. Functional MRI suggested that LDE225 causes increased tumor diffusion and works particularly well in patients with poor baseline perfusion. Clinical trial information: NCT02358161.

Diagnostic performance of T2-weighted imaging and intravoxel incoherent motion diffusion-weighted MRI for predicting metastatic axillary lymph nodes in T1 and T2 stage breast cancer.

Non-invasive modalities for assessing axillary lymph node (ALN) are needed in clinical practice. To investigate the suspicious ALN on unenhanced T2-weighted (T2W) imaging and intravoxel incoherent motion diffusion-weighted imaging (IVIM DWI) for predicting ALN metastases (ALNM) in patients with T1-T2 stage breast cancer and clinically negative ALN. Two radiologists identified the most suspicious ALN or the largest ALN in negative axilla by T2W imaging features, including short axis (Size-S), long axis (Size-L)/S ratio, fatty hilum, margin, and signal intensity on T2W imaging. The IVIM parameters of these selected ALNs were also obtained. The Mann-Whitney U test or t-test was used to compare the metastatic and non-metastatic ALN groups. Finally, logistic regression analysis with T2W imaging and IVIM features for predicting ALNM was conducted. This study included 49 patients with metastatic ALNs and 50 patients with non-metastatic ALNs. Using the above conventional features on T2W imaging, the sensitivity and specificity in predicting ALNM were not high. Compared with non-metastatic ALNs, metastatic ALNs had lower pseudo-diffusion coefficient (D*) (P = 0.043). Logistic regression analysis showed that the most useful features for predicting ALNM were signal intensity and D*. The sensitivity and specificity predicting ALNM that satisfied abnormal signal intensity and lower D* were 73.5% and 84%, respectively. The abnormal signal intensity on T2W imaging and one IVIM feature (D*) were significantly associated with ALNM, with sensitivity of 73.5% and specificity of 84%.

Intravoxel incoherent motion diffusion-weighted MRI for thecharacterization of inflammation in chronic liver disease.

To evaluate the diagnostic performance of intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) for grading hepatic inflammation. In this retrospective cross-sectional dual-center study, 91 patients with chronic liver disease were recruited between September 2014 and September 2018. Patients underwent 3.0-T MRI examinations within 6weeks from a liver biopsy. IVIM parameters, perfusion fraction (f), diffusion coefficient (D), and pseudo-diffusion coefficient (D*), were estimated using a voxel-wise nonlinear regression on DWI series (10 b-values from 0 to 800s/mm2). The reference standard was histopathological analysis of hepatic inflammation grade, steatosis grade, and fibrosis stage. Intraclass correlation coefficients (ICC), univariate and multivariate correlation analyses, and areas under receiver operating characteristic curves (AUC) were assessed. Parameters f, D, and D* had ICCs of 0.860, 0.839, and 0.916, respectively. Correlations of f, D, and D* with inflammation grade were ρ = - 0.70, p < 0.0001; ρ = 0.10, p = 0.35; and ρ = - 0.27, p = 0.010, respectively. When adjusting for fibrosis and steatosis, the correlation between f and inflammation (p < 0.0001) remained, and that between f and fibrosis was also significant to a lesser extent (p = 0.002). AUCs of f, D, and D* for distinguishing inflammation grades 0 vs. ≥ 1 were 0.84, 0.53, and 0.70; ≤ 1 vs. ≥ 2 were 0.88, 0.57, and 0.60; and ≤ 2 vs. 3 were 0.86, 0.54, and 0.65, respectively. Perfusion fraction f strongly correlated, D very weakly correlated, and D* weakly correlated with inflammation. Among all IVIM parameters, f accurately graded inflammation and showed promise as a biomarker of hepatic inflammation. • IVIM parameters derived from DWI series with 10 b-values are reproducible for liver tissue characterization. • This retrospective two-center study showed that perfusion fraction provided good diagnostic performance for distinguishing dichotomized grades of inflammation. • Fibrosis is a significant confounder on the association between inflammation and perfusion fraction.

Improving diagnostic performance of differentiating ocular adnexal lymphoma and idiopathic orbital inflammation using intravoxel incoherent motion diffusion-weighted MRI

PurposeTo investigate the utility of intravoxel incoherent motion diffusion-weighted MRI (IVIM-DWI) derived diffusion and perfusion parameters in differentiating ocular adnexal lymphoma (OAL) from idiopathic orbital inflammation (IOI), and to assess whether IVIM-DWI provides improved diagnostic performance for the distinction. MethodTwenty-one patients with OAL and 24 patients with IOI underwent IVIM-DWI. Apparent diffusion coefficient (ADC) and IVIM-DWI parameters including true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f) were measured in lesions by two independent radiologists. The MRI parameter differences between OAL and IOI were tested using two-sample t-test. The receiver operating characteristic (ROC) analysis curves were used to determine the diagnostic performance of significant parameters for differentiation between OAL and IOI. ResultsThe ADC, D, and f were lower in OAL than those in IOI (ADC = 0.78 ± 0.12 vs. 0.99 ± 0.16 × 10−3 mm2/s, P < 0.001; D = 0.34 ± 0.15 vs. 0.76 ± 0.25 × 10−3 mm2/s, P < 0.001; f = 0.31 ± 0.06 vs. 0.41 ± 0.08 × 100 %, P < 0.001). There was no significant difference in D* between OAL and IOI (P = 0.235). The optimal cut-off values of ADC, D, and f in differentiating OAL from IOI were 0.83 × 10-3 mm2/s, 0.56 × 10-3 mm2/s, and 0.36 × 100 %, respectively. No significant differences were found in areas under the curve (AUCs) among ADC, D and f (all P > 0.05). The combination of D and f provided significantly higher AUC than ADC (AUC = 0.984 vs. 0.838, Z = 2.128, P = 0.033), and had higher sensitivity of 95.24 %, specificity of 95.83 %, and accuracy of 95.56 %. ConclusionsIVIM-DWI is valuable in differentiating OAL from IOI, and D combined f can improve the performance of differential diagnosis.

Reproducibility of radiomics features derived from intravoxel incoherent motion diffusion-weighted MRI of cervical cancer.

The reproducibility of intravoxel incoherent motion (IVIM)-based radiomics studies in humans has not been reported. To determine the inter- and intra-observer variability on the reproducibility of IVIM-based radiomics features in cervical cancer (CC). The IVIM images of 25 patients with CC were retrospectively collected. Based on the high-resolution T2-weighted images, the regions of interest (ROIs) were independently delineated twice in diffusion-weighted images at a b value of 1000 s/mm2 (interval time was one month) by two radiologists. This was done at the largest transversal cross-sections of the tumors. The ROI was subsequently used in apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f) maps derived from IVIM images. In total, 105 radiomics features were then finally extracted from the IVIM-derived maps. The inter- and intra-observer reproducibility of IVIM-derived features was then evaluated using the intraclass correlation coefficient. Inter- and intra-observer variability affected the reproducibility of radiomics features. D* map had 100% and 95% reproducible features, ADC map had 89% and 93%, D map had 97% and 86%, while f map had 54% and 62% reproducible features with good to excellent reliability in the intra-observer analysis. Similarly, D* map had 90% and 94%, ADC map had 85% and 70%, D map had 81% and 78%, while f map had 41% and 93% reproducible features with good to excellent reliability in the inter-observer analysis. Inter- and intra-observer variability can affect radiomics analysis. Cognizant to this, multicenter studies should pay more attention to intra- and inter-observer variability.

Intravoxel Incoherent Motion Diffusion-weighted MRI of Infiltrated Marrow for Predicting Overall Survival in Newly Diagnosed Acute Myeloid Leukemia.

Background Acute myeloid leukemia (AML) features relatively low overall survival (OS). Intravoxel incoherent motion (IVIM) diffusion-weighted MRI separates tissue microcapillary perfusion and diffusivity and may have potential for helping to assess prognosis in infiltrated marrow disease apart from solid tumor. Thus, a study of overall survival would contribute to clarifying the value of IVIM for assessing long-term prognosis in AML. Purpose To determine whether the IVIM-derived parameters of infiltrated bone marrow may be associated with OS in newly diagnosed AML. Materials and Methods This prospective study enrolled participants with newly diagnosed AML between July 2014 to March 2016 consecutively. Participants underwent MRI of the lumbar spine by using an IVIM sequence. Participant clinical characteristics and OS were collected. The median of follow-up period was 20 months (range, 1-56 months). The IVIM parameters (pseudoperfusion fraction, f; diffusion coefficient, D; and pseudodiffusion coefficient, D*) were obtained. A nonparametric log-rank test was used to identify the threshold of IVIM parameters for OS. Univariable Kaplan-Meier and multivariable Cox proportional hazards regression analyses were performed to investigate prognostic significance of possible indicators. Results Fifty-three participants (mean age, 42 years ± 17; 30 men) were evaluated. Nonparametric log-rank test results showed that the thresholds of f and D values for OS were 31.0% and 0.2 × 10-3 mm2/sec, respectively. Univariable analyses indicated that high f value (>31.0%) and low D value (≤0.2 × 10-3 mm2/sec) were associated with shorter OS (P = .003 and .01, respectively). An f value greater than 31.0% (hazard ratio, 2.4; 95% confidence interval: 1.0, 5.6; P = .046) was associated with OS, independent of clinical confounders (age, karyotype, and white blood cell counts) in a multivariable analysis. Conclusion Pseudoperfusion fraction and diffusion coefficient from intravoxel incoherent motion diffusion-weighted MRI may be viable prognosis predictors of newly diagnosed acute myeloid leukemia. © RSNA, 2020.

Intravoxel incoherent motion diffusion-weighted MRI in patients with breast cancer: Correlation with tumor stroma characteristics

PurposeTo determine whether imaging parameters derived from intravoxel incoherent motion (IVIM) diffusion weighted imaging (DWI) vary according to tumor-stroma ratio(TSR) or dominant stroma type of breast cancer. MethodsWe prospectively enrolled 77 patients with breast cancer who underwent IVIM DWI on a 3.0 T MR scanner. The values of IVIM parameters (D, D* and f) were measured. After surgery, TSR or dominant stroma type was evaluated. The relationship between imaging parameters and tumor stroma characteristics was analyzed. ResultsThe mean D and f values were lower in stroma-poor tumor than in stroma-rich tumor (P = 0.012, 0.015). The mean D value was lower in the collagen-dominant type than in fibroblast-dominant or lymphocyte-dominant type (P = 0.032, 0.043). According to multivariate linear regression analyses, tumor size (P = 0.007), TSR (P = 0.008), dominant stroma type (collagen dominant, P = 0.012), and histological grade (P = 0.031) were independently correlated with D value; and tumor size (P = 0.011), TSR (P = 0.021) and histological grade (P = 0.037) were independently correlated with f value. ConclusionIn breast cancer, D and f values show significant differences according to TSR, and D value is lower in collagen dominant type than in fibroblast dominant or lymphocyte dominant types.