Intravoxel Incoherent Motion Perfusion Fraction Research Articles

Effect of Mediterranean diet or mindfulness-based stress reduction during pregnancy on placental volume and perfusion: A subanalysis of the IMPACT BCN randomized clinical trial.

The IMPACT BCN trial-a parallel-group randomized clinical trial where 1221 pregnant women at high risk for small-for-gestational age (SGA) newborns were randomly allocated at 19- to 23-week gestation into three groups: Mediterranean diet, Mindfulness-based Stress reduction or non-intervention-has demonstrated a positive effect of Mediterranean diet and Stress reduction in the prevention of SGA. However, the mechanism of action of these interventions remains still unclear. The aim of this study is to investigate the effect of Mediterranean diet and Stress reduction on placental volume and perfusion. Participants in the Mediterranean diet group received monthly individual and group educational sessions, and free provision of extra-virgin olive oil and walnuts. Women in the Stress reduction group underwent an 8-week Stress reduction program adapted for pregnancy, consisting of weekly 2.5-h and one full-day sessions. Non-intervention group was based on usual care. Placental volume and perfusion were assessed in a subgroup of randomly selected women (n = 165) using magnetic resonance (MR) at 36-week gestation. Small placental volume was defined as MR estimated volume <10th centile. Perfusion was assessed by intravoxel incoherent motion. While mean MR placental volume was similar among the study groups, both interventions were associated with a lower prevalence of small placental volume (3.9% Mediterranean diet and 5% stress reduction vs. 17% non-intervention; p = 0.03 and p = 0.04, respectively). Logistic regression showed that small placental volume was significantly associated with higher risk of SGA in both study groups (OR 7.48 [1.99-28.09] in Mediterranean diet and 20.44 [5.13-81.4] in Stress reduction). Mediation analysis showed that the effect of Mediterranean diet on SGA can be decomposed by a direct effect and an indirect effect (56.6%) mediated by a small placental volume. Similarly, the effect of Stress reduction on SGA is partially mediated (45.3%) by a small placental volume. Results on placental intravoxel incoherent motion perfusion fraction and diffusion coefficient were similar among the study groups. Structured interventions during pregnancy based on Mediterranean diet or Stress reduction are associated with a lower proportion of small placentas, which is consistent with the previously observed beneficial effects of these interventions on fetal growth.

MRI and Blood-based Biomarkers Are Associated With Surgery in Children and Adults With Ileal Crohn's Disease.

Despite advances in medical therapy, many children and adults with ileal Crohn's disease (CD) progress to fibrostenosis requiring surgery. We aimed to identify MRI and circulating biomarkers associated with the need for surgical management. This prospective, multicenter study included pediatric and adult CD cases undergoing ileal resection and CD controls receiving medical therapy. Noncontrast research MRI examinations measured bowel wall 3-dimensional magnetization transfer ratio normalized to skeletal muscle (normalized 3D MTR), modified Look-Locker inversion recovery (MOLLI) T1 relaxation, intravoxel incoherent motion (IVIM) diffusion-weighted imaging metrics, and the simplified magnetic resonance index of activity (sMaRIA). Circulating biomarkers were measured on the same day as the research MRI and included CD64, extracellular matrix protein 1 (ECM1), and granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies (Ab). Associations between MRI and circulating biomarkers and need for ileal resection were tested using univariate and multivariable LASSO regression. Our study sample included 50 patients with CD undergoing ileal resection and 83 patients with CD receiving medical therapy; mean participant age was 23.9 ± 13.1 years. Disease duration and treatment exposures did not vary between the groups. Univariate biomarker associations with ileal resection included log GM-CSF Ab (odds ratio [OR], 2.87; P = .0009), normalized 3D MTR (OR, 1.05; P = .002), log MOLLI T1 (OR, 0.01; P = .02), log IVIM perfusion fraction (f; OR, 0.38; P = .04), and IVIM apparent diffusion coefficient (ADC; OR, 0.3; P = .001). The multivariable model for surgery based upon correctedAkaike information criterion included age (OR, 1.03; P = .29), BMI (OR, 0.91; P = .09), log GM-CSF Ab (OR, 3.37; P = .01), normalized 3D MTR (OR, 1.07; P = .007), sMaRIA (OR, 1.14; P = .61), luminal narrowing (OR, 10.19; P = .003), log C-reactive protein (normalized; OR, 2.75; P = .10), and hematocrit (OR, 0.90; P = .13). After accounting for clinical and MRI measures of severity, normalized 3D MTR and GM-CSF Ab are associated with the need for surgery in ileal CD.

Intravoxel incoherent motion (IVIM)-derived perfusion fraction mapping for the visual evaluation of MR-guided high intensity focused ultrasound (MR-HIFU) ablation of uterine fibroids

Background A method for periprocedural contrast agent-free visualization of uterine fibroid perfusion could potentially shorten magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) treatment times and improve outcomes. Our goal was to test feasibility of perfusion fraction mapping by intravoxel incoherent motion (IVIM) modeling using diffusion-weighted MRI as method for visual evaluation of MR-HIFU treatment progression. Methods Conventional and T2-corrected IVIM-derived perfusion fraction maps were retrospectively calculated by applying two fitting methods to diffusion-weighted MRI data (b = 0, 50, 100, 200, 400, 600 and 800 s/mm2 at 1.5 T) from forty-four premenopausal women who underwent MR-HIFU ablation treatment of uterine fibroids. Contrast in perfusion fraction maps between areas with low perfusion fraction and surrounding tissue in the target uterine fibroid immediately following MR-HIFU treatment was evaluated. Additionally, the Dice similarity coefficient (DSC) was calculated between delineated areas with low IVIM-derived perfusion fraction and hypoperfusion based on CE-T1w. Results Average perfusion fraction ranged between 0.068 and 0.083 in areas with low perfusion fraction based on visual assessment, and between 0.256 and 0.335 in surrounding tissues (all p < 0.001). DSCs ranged from 0.714 to 0.734 between areas with low perfusion fraction and the CE-T1w derived non-perfused areas, with excellent intraobserver reliability of the delineated areas (ICC 0.97). Conclusion The MR-HIFU treatment effect in uterine fibroids can be visualized using IVIM perfusion fraction mapping, in moderate concordance with contrast enhanced MRI. IVIM perfusion fraction mapping has therefore the potential to serve as a contrast agent-free imaging method to visualize the MR-HIFU treatment progression in uterine fibroids.

Analysis of IVIM Perfusion Fraction Improves Detection of Pancreatic Ductal Adenocarcinoma.

The purpose of this study was to evaluate whether intravoxel incoherent motion (IVIM) parameters can enhance the diagnostic performance of MRI in differentiating normal pancreatic parenchyma from solid pancreatic adenocarcinomas. This study included 113 participants: 66 patients diagnosed with pancreatic adenocarcinoma and 47 healthy volunteers. An MRI was conducted at 1.5 T MR unit, using nine b-values. Postprocessing involved analyzing both conventional monoexponential apparent diffusion coefficient (ADC) and IVIM parameters (diffusion coefficient D-pure molecular diffusion coefficient, perfusion-dependent diffusion coefficient D*-pseudodiffusion coeffitient, and perfusion fraction coefficient (f)) across four different b-value selections. Significantly higher parameters were found in the control group when using high b-values for the pure diffusion analysis and all b-values for the monoexponential analysis. Conversely, in the study group, the parameters were affected by low b-values. Most parameters could differentiate between normal and cancerous tissue, with D* showing the highest diagnostic performance (AUC 98-100%). A marked decrease in perfusion in the patients with pancreatic cancer, indicated by the significant differences in the D* medians between groups, was found. In conclusion, standard ADC maps alone may not suffice for a definitive pancreatic cancer diagnosis, and incorporating IVIM into MRI protocols is recommended, as the reduced tissue perfusion detected by the IVIM parameters is a promising marker for pancreatic adenocarcinoma.

MRI AND BLOOD-BASED BIOMARKERS ASSOCIATED WITH SURGICAL MANAGEMENT IN CHILDREN AND ADULTS WITH SMALL BOWEL CROHN'S DISEASE

Abstract BACKGROUND Despite advances in medical therapy, many children and adults with ileal Crohn’s Disease (CD) progress to fibrostenosis requiring surgery. Prior studies have identified circulating and imaging biomarkers associated with strictures, although their associations with need for surgery are not well-established. PURPOSE We aimed to identify MRI and circulating biomarkers associated with the need for surgical management in chidlren and adults with ileal CD. METHODS This prospective, multi-center study included pediatric and adult CD cases undergoing ileal resection (n=50), and CD controls receiving medical therapy (n=83). Noncontrast research MRI examinations measured bowel wall three-dimensional magnetization transfer ratio normalized to skeletal muscle (normalized 3D MTR), modified Look-Locker inversion recovery (MOLLI) T1 relaxation, intravoxel incoherent motion (IVIM) diffusion-weighted imaging metrics, and the simplified magnetic resonance index of activity (sMaRIA) (Figure 1). Circulating biomarkers included CD64, ECM1, and GM-CSF autoantibodies (Ab). Clinical variables, including demographics, anthropometrics, and routine clinical laboratory data (e.g., CRP, fecal calprotectin), also were obtained at the research visit. Associations between MRI and circulating biomarkers and need for ileal resection were tested using univariate and multivariable LASSO regression. RESULTS Mean participant age was 23.9±13.1 years. Disease duration and treatment exposures did not vary between the groups. Univariate biomarker associations with ileal resection included log GM-CSF Ab (odds ratio [OR]=2.87; p=0.0009), normalized 3D MTR (OR=1.05; p=0.002), log MOLLI T1 (OR=0.01; p=0.02), log IVIM perfusion fraction (f) (OR=0.38; p=0.04), and IVIM apparent diffusion coefficient (ADC) (OR=0.3; p=0.001). MRI and circulating biomarker Tukey box plots are presented in Figure 2. The multivariable model for surgery based upon AICc criteria included age (OR=1.03; p=0.29), BMI (OR=0.91; p=0.09), log GM-CSF Ab (OR=3.37; p=0.01), normalized 3D MTR (OR=1.07; p=0.007), sMaRIA (OR=1.14; p=0.61), luminal narrowing (OR=10.19; p=0.003), log CRP (normalized) (OR=2.75; p=0.10), and hematocrit (OR=0.90; p=0.13). CONCLUSION After accounting for clinical and MRI measures of severity, normalized 3D MTR and GM-CSF Ab are associated with need for surgery in ileal CD. GM-CSF autoantibodies and MRI biomarker sequences may be useful for guiding management decisions in CD patients. Figure 1 Research MRI images from a surgical Crohn’s disease patient with stricturing behavior involving the terminal ileum. A and B. Coronal and axial fat-saturated T2-weighted single-shot fast spin-echo (SSFSE) images show wall thickening and luminal narrowing of the terminal ileum (arrows) with more proximal bowel dilation measuring greater than 3 cm. C. Axial 3D magnetization transfer images – MT pulse on (bottom image, arrow), MT pulse off (top image, arrow). D. Axial modified Look-Locker inversion recovery (MOLLI) T1 relaxation image (arrow). E. Representative axial intravoxel incoherent motion diffusion-weighted images with increasing b-values (left to right, arrows). Figure 2 Variation in circulating and imaging biomarkers in Crohn’s disease patients with medical and surgical management. Ctrl: non-IBD healthy controls; Med: CD patients with nonsurgical medical management; Surg: CD patients with surgical management.

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.

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. 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. Phantom repeatability. 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. Bipolar gradient twice-refocused spin echo sequence and monopolar gradient single spin echo sequence at 3 T. 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. 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. 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. 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. 2 TECHNICAL EFFICACY: Stage 1.

Intravoxel Incoherent Motion MRI and PET in Locally Advanced Cervical Carcinoma Undergoing Concurrent Chemoradiation Therapy

<h3>Purpose/Objective(s)</h3> Dynamic contrast enhanced (DCE) CT or MRI and FDG PET have been used to evaluate the impact of tumor perfusion and metabolism on the course and effectiveness of concurrent chemoradiation therapy (CCRT) for cervical cancer. Combining perfusion and metabolic measures allows better identification of radioresistant sub-volumes: however, use of contrast and additional dose are barriers to frequent dual perfusion-metabolic imaging. Here, we investigated a contrast-free, non-ionizing alternative to DCE: intravoxel incoherent motion (IVIM) MRI which provides both perfusion and diffusion measurements. Our objective was to evaluate changes of PET and IVIM parameters in cervical cancer patients before and during CCRT and to correlate these parameters and their changes with tumor volume response during CCRT. <h3>Materials/Methods</h3> Pre- and on-treatment IVIM scans were performed on 15 cervical cancer patients undergoing definitive chemoradiation (median [range] age: 66 [29 to 85]; FIGO: 1 IB1, 1 IIA, 3 IIB, 1 IIIB, 1 IIIC, 5 IIIC1, 2 IIIC2, 1 IVA; hist: 11 squamous cell carcinoma, 3 endocervical adenocarcinoma, 1 large cell neuroendocrine carcinoma), of whom 14 also underwent pre-treatment PET scans. The on-treatment MRI occurred generally during the last week or shortly after completing EBRT. Diffusion weighted images (DWIs) were acquired at 3T scanners using a free-breathing single shot spin echo planar imaging (EPI) sequence. IVIM MRI maps were generated by Bayesian fitting of a two-compartment IVIM model to the DWIs. Three-dimensional co-registered maps of PET standardized uptake value (SUV) and IVIM diffusion coefficient (D), perfusion fraction (f), and pseudo-diffusion coefficient (D*) were generated. Summary statistics (mean +/- standard deviation) for these and other imaging parameters were calculated pre- and on-treatment. Univariate analysis was performed to determine relationships between relative change in gross tumor volume (ΔGTV) and pre-treatment imaging measurements. <h3>Results</h3> In tumors, pre- versus on-treatment values significantly changed for the following parameters: ΔGTV (66.8 +/- 43.2 vs. 32.0+/-23.0 ml, p<.001) and D (0.00109 +/- 0.00023 vs. 0.00120 +/- 0.00026 mm²/s, p=.02). The perfusion fraction f increased and D* decreased, but not significantly (f: 0.127 +/- 0.022 vs. 0.154 +/- 0.057 %, p=.07, D*: 0.0137 +/- 0.0035 vs. 0.0133 +/- 0.0039 mm²/s, p=.6). Pre-treatment SUV_max (r=.76, p=.002) and SUV_mean (r=.70, p=.007) were positively related with ΔGTV, while pre-treatment f, D*, and D were negatively but not significantly related with ΔGTV (r=-.44, p=.1; D*: r=-.14, p=.6; D: r=-.12, p=.7). <h3>Conclusion</h3> Both perfusion fraction and diffusion coefficient IVIM increased in locally advanced cervical carcinoma patients undergoing CCRT – reflecting changes in the tumor microenvironment during treatment. These weak relationships observed here suggest a potential complementary role and motivating the combined use of these modalities for tumor characterization.

Differentiating False Positive Lesions from Clinically Significant Cancer and Normal Prostate Tissue Using VERDICT MRI and Other Diffusion Models.

False positives on multiparametric MRIs (mp-MRIs) result in many unnecessary invasive biopsies in men with clinically insignificant diseases. This study investigated whether quantitative diffusion MRI could differentiate between false positives, true positives and normal tissue non-invasively. Thirty-eight patients underwent mp-MRI and Vascular, Extracellular and Restricted Diffusion for Cytometry in Tumors (VERDICT) MRI, followed by transperineal biopsy. The patients were categorized into two groups following biopsy: (1) significant cancer—true positive, 19 patients; (2) atrophy/inflammation/high-grade prostatic intraepithelial neoplasia (PIN)—false positive, 19 patients. The clinical apparent diffusion coefficient (ADC) values were obtained, and the intravoxel incoherent motion (IVIM), diffusion kurtosis imaging (DKI) and VERDICT models were fitted via deep learning. Significant differences (p < 0.05) between true positive and false positive lesions were found in ADC, IVIM perfusion fraction (f) and diffusivity (D), DKI diffusivity (DK) (p < 0.0001) and kurtosis (K) and VERDICT intracellular volume fraction (fIC), extracellular–extravascular volume fraction (fEES) and diffusivity (dEES) values. Significant differences between false positives and normal tissue were found for the VERDICT fIC (p = 0.004) and IVIM D. These results demonstrate that model-based diffusion MRI could reduce unnecessary biopsies occurring due to false positive prostate lesions and shows promising sensitivity to benign diseases.

Different hemodynamics of basal ganglia between moyamoya and non-moyamoya diseases using intravoxel incoherent motion imaging and single-photon emission computed tomography.

Moyamoya disease (MMD) and non-MMD have different pathogenesis, clinical presentation, and treatment policy. To identify differences in hemodynamics between MMD and non-MMD using intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT). Patients who had undergone 99mTc-ECD or 123I-IMP SPECT, and IVIM imaging were retrospectively studied. IVIM imaging was acquired using six different b-values. Cerebral blood flow ratio (CBFR) in the basal ganglia was calculated using a standardized volume-of-interest template. The cerebellum was used as a reference region. IVIM perfusion fraction (f) was obtained using a two-step fitting algorithm. Elliptical regions of interest were placed in bilateral basal ganglia on the IVIM f map. Patients were classified into MMD and non-MMD groups. The correlation between CBFR and mean IVIM f (fmean) in the basal ganglia was evaluated using Spearman's rank correlation coefficient. In total, 20 patients with MMD and 28 non-MMD patients were analyzed. No significant differences in fmean were observed among MMD, affected hemisphere with non-MMD (non-MMDaff), and unaffected hemispheres with non-MMD (non-MMDunaff). A negative correlation was seen between fmean and CBFR in the MMD group (r = -0.40, P = 0.0108), but not in the non-MMD group (non-MMDaff, r = 0.07, P = 0.69; non-MMDunaff, r = -0.22, P = 0.29). No significant differences were found among MMD and non-MMD patients, irrespective of SPECT tracers. The combination of IVIM MRI and SPECT appears to allow non-invasive identification of differences in hemodynamics between MMD and non-MMD.

Interobserver Reliability on Intravoxel Incoherent Motion Imaging in Patients with Acute Ischemic Stroke.

Noninvasive perfusion-weighted imaging with short scanning time could be advantageous in order to determine presumed penumbral regions and subsequent treatment strategy for acute ischemic stroke (AIS). Our aim was to evaluate interobserver agreement and the clinical utility of intravoxel incoherent motion MR imaging in patients with acute ischemic stroke. We retrospectively studied 29 patients with AIS (17 men, 12 women; mean age, 75.2 [SD, 12.0 ] years; median, 77 years). Each patient underwent intravoxel incoherent motion MR imaging using a 1.5T MR imaging scanner. Diffusion-sensitizing gradients were applied sequentially in the x, y, and z directions with 6 different b-values (0, 50, 100, 150, 200, and 1000 seconds/mm2). From the intravoxel incoherent motion MR imaging data, diffusion coefficient, perfusion fraction, and pseudodiffusion coefficient maps were obtained using a 2-step fitting algorithm based on the Levenberg-Marquardt method. The presence of decreases in the intravoxel incoherent motion perfusion fraction and pseudodiffusion coefficient values compared with the contralateral normal-appearing brain was graded on a 2-point scale by 2 independent neuroradiologists. Interobserver agreement on the rating scale was evaluated using the κ statistic. Clinical characteristics of patients with a nondecreased intravoxel incoherent motion perfusion fraction and/or pseudodiffusion coefficient rated by the 2 observers were also assessed. Interobserver agreement was shown for the intravoxel incoherent motion perfusion fraction (κ = 0.854) and pseudodiffusion coefficient (κ = 0.789) maps, which indicated almost perfect and substantial agreement, respectively. Patients with a nondecreased intravoxel incoherent motion perfusion fraction tended to show recanalization of the occluded intracranial arteries more frequently than patients with a decreased intravoxel incoherent motion perfusion fraction. Intravoxel incoherent motion MR imaging could be performed in < 1 minute in addition to routine DWI. Intravoxel incoherent motion parameters noninvasively provide feasible, qualitative perfusion-related information for assessing patients with acute ischemic stroke.

Investigation of breast cancer microstructure and microvasculature from time-dependent DWI and CEST in correlation with histological biomarkers

We investigated the associations of time-dependent DWI, non-Gaussian DWI, and CEST parameters with histological biomarkers in a breast cancer xenograft model. 22 xenograft mice (7 MCF-7 and 15 MDA-MB-231) were scanned at 4 diffusion times [Td = 2.5/5 ms with 11 b-values (0–600 s/mm2) and Td = 9/27.6 ms with 17 b-values (0–3000 s/mm2), respectively]. The apparent diffusion coefficient (ADC) was estimated using 2 b-values in different combinations (ADC0–600 using b = 0 and 600 s/mm2 and shifted ADC [sADC200–1500] using b = 200 and 1500 s/mm2) at each of those diffusion times. Then the change (Δ) in ADC/sADC between diffusion times was evaluated. Non-Gaussian diffusion and intravoxel incoherent motion (IVIM) parameters (ADC0, the virtual ADC at b = 0; K, Kurtosis from non-Gaussian diffusion; f, the IVIM perfusion fraction) were estimated. CEST images were acquired and the amide proton transfer signal intensity (APT SI) were measured. The ΔsADC9–27.6 (between {text{sADC}}_{{9,{text{ms}}}}^{200{-}1500} and {text{sADC}}_{{27.6,{text{ms}}}}^{200{-}1500} and ΔADC2.5_sADC27.6 (between {text{ADC}}_{{2.5, {text{ms}}}}^{0{-}600} and {text{sADC}}_{{27.6,{text{ms}}}}^{200{-}1500}) was significantly larger for MCF-7 groups, and ΔADC2.5_sADC27.6 was positively correlated with Ki67max and APT SI. ADC0 decreased significantly in MDA-MB-231 group and K increased significantly with Td in MCF-7 group. APT SI and cellular area had a moderately strong positive correlation in MDA-MB-231 and MCF-7 tumors combined, and there was a positive correlation in MDA-MB-231 tumors. There was a significant negative correlation between APT SI and the Ki-67-positive ratio in MDA-MB-231 tumors and when combined with MCF-7 tumors. The associations of ΔADC2.5_sADC27.6 and API SI with Ki-67 parameters indicate that the Td-dependent DW and CEST parameters are useful to predict the histological markers of breast cancers.

IntraVoxel Incoherent Motion (IVIM) MRI of fetal lung and kidney: Can the perfusion fraction be a marker of normal pulmonary and renal maturation?

PurposeTo investigate the use of IntraVoxel Incoherent Motion (IVIM) MRI in the study of microstructural tissue changes occurring in fetal lung and kidney during gestation. Methods34 normal pregnancies were enrolled. Patients were divided into two groups based on gestational age (GA): group A (21−29 weeks) and group B (30−39 weeks). MR examinations were performed at 1.5T, with a standard fetal MR protocol including a Diffusion-Weighted Echo-Planar Imaging sequence with 10 different b-values (0, 10, 30, 50, 75, 100, 200, 400, 700, 1000s/mm2). For each fetus, two bilateral ROIs were manually placed in lung and renal parenchyma. Mean values of perfusion fraction f, pseudo-diffusion coefficient D* and diffusion coefficient D were obtained. The correlation between IVIM parameters and GA was investigated. ResultsIn renal ROIs a positive correlation between fkidney and GA (p < 0.005) was found; similarly flung showed a statistically significant correlation with GA (p < 0.001). F mean values were significantly higher in group B compared to group A in both renal (p = 0.0002) and lung (p = 0.018) ROIs. No correlation was found in D and D* as a function of GA. ConclusionsThe IVIM perfusion fraction f may be considered as a potential marker of pulmonary and renal maturation in relation to hemodynamic changes described in intrauterine life. Our results highlight that IVIM model is useful as an additional prenatal diagnostic tool to study lung and renal development.

Association between IVIM parameters and treatment response in locally advanced squamous cell cervical cancer treated by chemoradiotherapy.

To examine the associations of intravoxel incoherent motion (IVIM) parameters with treatment response in cervical cancer following concurrent chemoradiotherapy (CCRT). Forty-five patients, median age of 58 years (range: 28-82), with pre-CCRT and post-CCRT MRI, were retrospectively analysed. The IVIM parameters pure diffusion coefficient (D) and perfusion fraction (f) were estimated using the full b-value distribution (BVD) as well as an optimised subsample BVD. Dice similarity coefficient (DSC) and intraclass correlation coefficient (ICC) were used to measure observer repeatability in tumour delineation at both time points. Treatment response was determined by the response evaluation criteria in solid tumour (RECIST) 1.1 between MRI examinations. Mann-Whitney U tests were used to test for significant differences in IVIM parameters between treatment response groups. Pre-CCRT tumour delineation repeatability was good (DSC = 0.81) while post-CCRT delineation repeatability was moderate (DSC = 0.67). Values of D and f had good repeatability at both time points (ICC > 0.80). Pre-CCRT f estimated using the full BVD and optimised subsample BVD were found to be significantly higher in patients with partial response compared to those with stable disease or disease progression (p = 0.01 and 95% CI = -0.02-0.00 for both cases). Pre-CCRT f was associated with treatment response in cervical cancer with good observer repeatability. Similar discriminative ability was also observed in estimated pre-CCRT f from an optimised subsample BVD. • Pre-treatment tumour delineation and IVIM parameters had good observer repeatability. • Post-treatment tumour delineation was worse than at pre-treatment, but IVIM parameters retained good ICC. • Pre-treatment perfusion fraction estimated from all b-values and an optimised subsample of b-values were associated with treatment response.

Advanced diffusion imaging of abdominal organs in different hydration states of the human body: stability of biomarkers

BackgroundMR diffusion weighted imaging (DWI) may provide important information regarding the pathophysiology of parenchymal abdominal organs. The purpose of our study was to investigate the stability of imaging biomarkers of diffusion weighted imaging (DWI), intravoxel incoherent motion (IVIM) and diffusion kurtosis imaging (DKI) in abdominal parenchymal organs regarding two body hydration states. MethodsTen healthy volunteers twice underwent DWI of abdominal organs using a double-refocused spin-echo echo-planar imaging sequences with 11 different b-values (ranging from 0 to 1,500 s/mm2): after 4 h of fluid deprivation; 45 min following 1000 ml of water intake. Four different diffusion models were evaluated and compared: standard DWI, DKI with mono-exponential fitting, multistep algorithm with variable b-value threshold for IVIM, combined IVIM-Kurtosis; in four abdominal organs: kidneys, liver, spleen and psoas muscle. ResultsDiffusion parameters from all four models remained similar for the renal parenchyma before and after the water challenge. Significant differences were found for the liver, spleen, and psoas muscle. The largest effects were seen for: the liver parenchyma after the water challenge by means of IVIM model's true diffusion (p < 0.02); the spleen, for IVIM's perfusion fraction (p < 0.03), the psoas muscle for the ADC value (p < 0.02). ConclusionsHerein, we showed that diffusion parameters of the kidney remain remarkably stable regarding the hydration status. This may be attributed to the kidney-specific compensatory mechanisms. For the liver, spleen and psoas muscle the diffusion parameters were sensitive to changes of the hydration. This phenomenon needs to be considered when evaluating diffusion data of these organs.

Diagnostic Performance of Diffusion MRI for differentiating Benign and Malignant Nonfatty Musculoskeletal Soft Tissue Tumors: A Systematic Review and Meta-analysis.

Objective: To evaluate the diagnostic performance of standard diffusion-weighted imaging (DWI), intravoxel incoherent motion (IVIM), and diffusion kurtosis imaging (DKI), for differentiating benign and malignant soft tissue tumors (STTs).Materials and methods: A thorough search was carried out to identify suitable studies published up to September 2020. The quality of the studies involved was evaluated using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). The pooled sensitivity (SEN), specificity (SPE), and summary receiver operating characteristic (SROC) curve were calculated using bivariate mixed effects models. A subgroup analysis was also performed to explore the heterogeneity.Results: Eighteen studies investigating 1319 patients with musculoskeletal STTs (malignant, n=623; benign, n=696) were enrolled. Thirteen standard DWI studies using the apparent diffusion coefficient (ADC) showed that the pooled SEN and SPE of ADC were 0.80 (95% CI: 0.77-0.82) and 0.63 (95% CI: 0.60-0.67), respectively. The area under the curve (AUC) calculated from the SROC curve was 0.806. The subgroup analysis indicated that the percentage of myxoid malignant tumors, magnet strength, study design, and ROI placement were significant factors affecting heterogeneity. Four IVIM studies showed that the AUCs calculated from the SROC curves of the parameters ADC and D were 0.859 and 0.874, respectively. The AUCs for the IVIM parameters pseudo diffusion coefficient (D*) and perfusion fraction (f) calculated from the SROC curve were 0.736 and 0.573, respectively. Two DKI studies showed that the AUCs of the DKI parameter mean kurtosis (MK) were 0.97 and 0.89, respectively.Conclusion: The DWI-derived ADC value and the IVIM DWI-derived D value might be accurate tools for discriminating musculoskeletal STTs, especially for non-myxoid SSTs, using more than two b values, with maximal b value ranging from 600 to 800 s/mm2, additionally, a high-field strength (3.0 T) optimizes the diagnostic performance.

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.

Intravoxel incoherent motion MRI in evaluating inflammatory activity in ulcerative colitis: a pilot study.

A non-invasive tool for the assessment of ulcerative colitis (UC) activity is needed for treatment control. To determine the efficacy of intravoxel incoherent motion (IVIM) in assessing inflammatory activity in UC. In this prospective study, 20 adult patients underwent 3.0-T magnetic resonance imaging (MRI) IVIM diffusion-weighted imaging (DWI) with 10 b-values (0-900 s/mm2) 0-6 days after biopsies entailing colonoscopy. The inflammatory activity of large bowel segments was graded on endoscopy with Mayo score and on pathology with a six‑grade classification system. IVIM‑derived parameters (f, D, and D*) calculated from regions of interest placed within the bowel wall were correlated with both scores (56 and 34 bowel segments, respectively). Radiologists were blinded to endoscopy and pathology results. A T-test and Wilcoxon rank sum test was used in comparisons and receiver operating characteristic curve analysis was performed. Statistically significant differences were found between histopathologically inactive or mild activity and moderate to severe activity in f (respectively: mean = 0.19 and mean = 0.28, P = 0.024; area under the curve [AUC] = 0.723, sensitivity 0.82, specificity 0.59, accuracy 0.67 for a 0.185 cut-off value) and D (mean = 1.34 × 10-3mm2/s and mean = 1.07 × 10-3mm2/s, P = 0.0083; AUC = 0.735, sensitivity 0.91, specificity 0.54, accuracy 0.66 for cut-off value 1.24 × 10-3mm2/s). No significant difference in D* was noted. No significant correlation between Mayo endoscopic subscore, and f, D, nor D* was found. IVIM perfusion fraction correlates with UC activity and might represent emerging tool in assessment of inflammatory activity.

Effect of granulocyte colony-stimulating factor on bone marrow: evaluation by intravoxel incoherent motion and dynamic contrast-enhanced magnetic resonance imaging.

To report our experience with the use of intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) and dynamic contrast-enhanced (DCE)-MRI in bone marrow before and after administration of granulocyte colony-stimulating factor (GCSF). Moreover, a small series of patients with bone metastases from breast cancer have been evaluated by IVIM DW-MRI and DCE-MRI before and after GCSF administration. We studied with IVIM-MRI and DCE-MRI 14 patients with rectal or uterine cervix cancer studied before and 4-18days after administration of GCSF; the second MR examination was obtained after three chemotherapy courses. IVIM perfusion fraction (f), pseudo-diffusion coefficient (D*), true diffusion coefficient (D) and apparent diffusion coefficient (ADC) as well area under the curve at 60s (AUC60) were calculated for bone marrow before and after GCSF administration. Moreover, two different IVIM parametric maps (i.e., ADC and ADClow) were generated by selecting two different intervals of b values (0-1000 and 0-80, respectively). Furthermore, four patients affected by pelvic bone metastases from breast adenocarcinoma who received GCSF administration were also qualitatively evaluated for evidence of lesions on ADC maps, ADClow maps and DCE-MRI. ADC, D, D*, f and AUC60 values were significantly higher in hyperplastic bone marrow than in untreated bone marrow (p values < 0.0001, < 0.0001, < 0.001, < 0.001, < 0.0001, respectively). All bone metastases were clearly differentiable from hyperplastic bone marrow on ADClow maps, but not on ADC maps and DCE-MRI. MR functional imaging techniques, such as DW-, IVIM DW- and DCE-MRI are effective tools in assessing the response of bone marrow to the administration of growth factors. Although an overlap between signal of hyperplastic bone marrow and lytic bone metastases can occur on ADC maps and DCE-MRI, evaluation of ADClow maps by IVIM DW-MRI could permit to differentiate hyperplastic bone marrow from lytic bone metastases. Further studies are needed to confirm our data.

Optimized Combination of b‑values for IVIM Perfusion Imaging in Acute Ischemic Stroke Patients.

To determine the optimal combination of low b‑values to generate perfusion information from intravoxel incoherent motion (IVIM) in patients with acute ischemic stroke (AIS) considering the time constraints for these patients. A retrospective cohort study of AIS patients with IVIM MRI was performed. A two-step voxel-by-voxel postprocessing was used to derive IVIM perfusion fraction maps with different combinations of bvalues. Signal values within regions of ischemic core, non-infarcted ischemic hemisphere, and contralateral hemisphere were measured on IVIM (f, D*, fD*, D) parameter maps. Bland-Altman analysis and the Dice similarity coefficient were used to determine quantitative and spatial agreements between the reference standard IVIM (IVIM with 6 bvalues of 0, 50, 100, 150, 200, 1000 s/mm2) and other combinations of bvalues. Significance level was set at p < 0.05. There were 58 patients (36males, 61.3%; mean age 70.2 ± 13.4 years) included. Considering all IVIM parameters, the combination of bvalues of 0, 50, 200, 1000 was the most consistent with our reference standard on Bland-Altman analysis. The best voxel-based overlaps of ischemic regions were on IVIMD, while there were good voxel-based overlaps on IVIMf. The IVIM with these four bvalues collects diffusion and perfusion information from asingle short MRI sequence, which may have important implications for the imaging of AIS patients.

Accelerated Segmented Diffusion-Weighted Prostate Imaging for Higher Resolution, Higher Geometric Fidelity, and Multi-b Perfusion Estimation.

The aim of this study was to improve the geometric fidelity and spatial resolution of multi-b diffusion-weighted magnetic resonance imaging of the prostate. An accelerated segmented diffusion imaging sequence was developed and evaluated in 25 patients undergoing multiparametric magnetic resonance imaging examinations of the prostate. A reduced field of view was acquired using an endorectal coil. The number of sampled diffusion weightings, or b-factors, was increased to allow estimation of tissue perfusion based on the intravoxel incoherent motion (IVIM) model. Apparent diffusion coefficients measured with the proposed segmented method were compared with those obtained with conventional single-shot echo-planar imaging (EPI). Compared with single-shot EPI, the segmented method resulted in faster acquisition with 2-fold improvement in spatial resolution and a greater than 3-fold improvement in geometric fidelity. Apparent diffusion coefficient values measured with the novel sequence demonstrated excellent agreement with those obtained from the conventional scan (R = 0.91 for bmax = 500 s/mm and R = 0.89 for bmax = 1400 s/mm). The IVIM perfusion fraction was 4.0% ± 2.7% for normal peripheral zone, 6.6% ± 3.6% for normal transition zone, and 4.4% ± 2.9% for suspected tumor lesions. The proposed accelerated segmented prostate diffusion imaging sequence achieved improvements in both spatial resolution and geometric fidelity, along with concurrent quantification of IVIM perfusion.