Intravoxel Incoherent Motion Perfusion Research Articles

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.

Quantitative perfusion and water transport time model from multi b-value diffusion magnetic resonance imaging validated against neutron capture microspheres.

Quantification of perfusion in ml/100 g/min, rather than comparing relative values side-to-side, is critical at the clinical and research levels for large longitudinal and multi-center trials. Intravoxel incoherent motion (IVIM) is a non-contrast magnetic resonance imaging diffusion-based scan that uses a multitude of -values to measure various speeds of molecular perfusion and diffusion, sidestepping inaccuracy of arterial input functions or bolus kinetics. Questions remain as to the original of the signal and whether IVIM returns quantitative and accurate perfusion in a pathology setting. This study tests a novel method of IVIM perfusion quantification compared with neutron capture microspheres. We derive an expression for the quantification of capillary blood flow in ml/100 g/min by solving the three-dimensional Gaussian probability distribution and defining water transport time (WTT) as when 50% of the original water remains in the tissue of interest. Calculations were verified in a six-subject pre-clinical canine model of normocapnia, induced hypercapnia, and middle cerebral artery occlusion (ischemic stroke) and compared with quantitative microsphere perfusion. Linear regression analysis of IVIM and microsphere perfusion showed agreement (slope = 0.55, intercept = 52.5, ) with a Bland-Altman mean difference of . Linear regression between dynamic susceptibility contrast mean transit time and IVIM WTT asymmetry in infarcted tissue was excellent (, intercept = 0.3, ). Strong linear agreement was found between IVIM and reference standard infarct volume (slope = 1.01, ). The simulation of cerebrospinal fluid (CSF) suppression via inversion recovery returned a blood signal reduced by 82% from combined T1 and T2 effects. The accuracy and sensitivity of IVIM provides evidence that observed signal changes reflect cytotoxic edema and tissue perfusion and can be quantified with WTT. Partial volume contamination of CSF may be better removed during post-processing rather than with inversion recovery.

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.

Signal to noise and b-value analysis for optimal intra-voxel incoherent motion imaging in the brain.

Intravoxel incoherent motion (IVIM) is a method that can provide quantitative information about perfusion in the human body, in vivo, and without contrast agent. Unfortunately, the IVIM perfusion parameter maps are known to be relatively noisy in the brain, in particular for the pseudo-diffusion coefficient, which might hinder its potential broader use in clinical applications. Therefore, we studied the conditions to produce optimal IVIM perfusion images in the brain. IVIM imaging was performed on a 3-Tesla clinical system in four healthy volunteers, with 16 b values 0, 10, 20, 40, 80, 110, 140, 170, 200, 300, 400, 500, 600, 700, 800, 900 s/mm2, repeated 20 times. We analyzed the noise characteristics of the trace images as a function of b-value, and the homogeneity of the IVIM parameter maps across number of averages and sub-sets of the acquired b values. We found two peaks of noise of the trace images as function of b value, one due to thermal noise at high b-value, and one due to physiological noise at low b-value. The selection of b value distribution was found to have higher impact on the homogeneity of the IVIM parameter maps than the number of averages. Based on evaluations, we suggest an optimal b value acquisition scheme for a 12 min scan as 0 (7), 20 (4), 140 (19), 300 (9), 500 (19), 700 (1), 800 (4), 900 (1) s/mm2.

Assessment of Impaired Cerebrovascular Reactivity in Chronic Cerebral Ischemia using Intravoxel Incoherent Motion Magnetic Resonance Imaging

BackgroundThe severity of chronic cerebral ischemia can be assessed using cerebrovascular reactivity (CVR) to acetazolamide (ACZ) challenge, which is measured by single-photon emission computed tomography (SPECT); however, this is an invasive method. We investigated whether intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) can assess impaired CVR in preoperative patients with chronic cerebral ischemia and compared it to SPECT-CVR. MethodsForty-seven patients with unilateral cervical carotid artery stenosis underwent diffusion-weighted MRI with 11 b-values in the range of 0–800 s/mm2 and cerebral perfusion SPECT with the ACZ challenge. The perfusion fraction (f) and diffusion coefficient (D) of the IVIM parameters were calculated using a bi-exponential model. The f and D values and these ratios of the ipsilateral middle cerebral artery territory against the contralateral side were compared with the CVR values of the affected side calculated from the SPECT data. ResultsThe IVIM-f and D values in the affected side were significantly higher than those in the unaffected side (median: 7.74% vs. 7.45%, p = 0.027; 0.816 vs. 0.801 10−3mm2/s, p < 0.001; respectively). However, there were no significant correlations between the f or D values and SPECT-CVR values in the affected side. In contrast, the f ratio showed a moderate negative correlation with the SPECT-CVR values (r = -0.40, p = 0.006) and detected impaired CVR (< 18.4%) with a sensitivity/specificity of 0.71/0.90. ConclusionThe IVIM perfusion parameter, f, can noninvasively assess impaired CVR with high sensitivity and specificity in patients with unilateral cervical carotid artery stenosis.

Daily Intravoxel Incoherent Motion (IVIM) In Prostate Cancer Patients During MR-Guided Radiotherapy-A Multicenter Study.

PurposeDaily quantitative MR imaging during radiotherapy of cancer patients has become feasible with MRI systems integrated with linear accelerators (MR-linacs). Quantitative images could be used for treatment response monitoring. With intravoxel incoherent motion (IVIM) MRI, it is possible to acquire perfusion information without the use of contrast agents. In this multicenter study, daily IVIM measurements were performed in prostate cancer patients to identify changes that potentially reflect response to treatment.Materials and MethodsForty-three patients were included, treated with 20 fractions of 3 Gy on a 1.5 T MR-linac. IVIM measurements were performed on each treatment day. The diffusion coefficient (D), perfusion fraction (f), and pseudo-diffusion coefficient (D*) were calculated based on the median signal intensities in the non-cancerous prostate and the tumor. Repeatability coefficients (RCs) were determined based on the first two treatment fractions. Separate linear mixed-effects models were constructed for the three IVIM parameters.ResultsIn total, 726 fractions were analyzed. Pre-treatment average values, measured on the first fraction before irradiation, were 1.46 × 10−3 mm2/s, 0.086, and 28.7 × 10−3 mm2/s in the non-cancerous prostate and 1.19 × 10−3 mm2/s, 0.088, and 28.9 × 10−3 mm2/s in the tumor, for D, f, and D*, respectively. The repeatability coefficients for D, f, and D* in the non-cancerous prostate were 0.09 × 10−3 mm2/s, 0.05, and 15.3 × 10−3 mm2/s. In the tumor, these values were 0.44 × 10−3 mm2/s, 0.16, and 76.4 × 10−3 mm2/s. The mixed effects analysis showed an increase in D of the tumors over the course of treatment, while remaining stable in the non-cancerous prostate. The f and D* increased in both the non-cancerous prostate and tumor.ConclusionsIt is feasible to perform daily IVIM measurements on an MR-linac system. Although the repeatability coefficients were high, changes in IVIM perfusion parameters were measured on a group level, indicating that IVIM has potential for measuring treatment response.

Assessment of Imaging Modalities Against Liver Biopsy in Nonalcoholic Fatty Liver Disease: The Amsterdam NAFLD‐NASH Cohort

BackgroundNoninvasive diagnostic methods are urgently required in disease stratification and monitoring in nonalcoholic fatty liver disease (NAFLD). Multiparametric magnetic resonance imaging (MRI) is a promising technique to assess hepatic steatosis, inflammation, and fibrosis, potentially enabling noninvasive identification of individuals with active and advanced stages of NAFLD.PurposeTo examine the diagnostic performance of multiparametric MRI for the assessment of disease severity along the NAFLD disease spectrum with comparison to histological scores.Study TypeProspective, cohort.PopulationThirty‐seven patients with NAFLD.Field Strength/SequenceMultiparametric MRI at 3.0 T consisted of magnetic resonance (MR) spectroscopy (MRS) with multi‐echo stimulated‐echo acquisition mode, magnitude‐based and three‐point Dixon using a two‐dimensional multi‐echo gradient echo, MR elastography (MRE) using a generalized multishot gradient‐recalled echo sequence and intravoxel incoherent motion (IVIM) using a multislice diffusion weighted single‐shot echo‐planar sequence.AssessmentHistological steatosis grades were compared to proton density fat fraction measured by MRS (PDFFMRS), magnitude‐based MRI (PDFFMRI‐M), and three‐point Dixon (PDFFDixon), as well as FibroScan® controlled attenuation parameter (CAP). Fibrosis and disease activity were compared to IVIM and MRE. FibroScan® liver stiffness measurements were compared to fibrosis levels. Diagnostic performance of all imaging parameters was determined for distinction between simple steatosis and nonalcoholic steatohepatitis (NASH).Statistical TestsSpearman's rank test, Kruskal–Wallis test, Dunn's post‐hoc test with Holm‐Bonferroni P‐value adjustment, receiver operating characteristic curve analysis. A P‐value <0.05 was considered statistically significant.ResultsHistological steatosis grade correlated significantly with PDFFMRS (r s = 0.66, P < 0.001), PDFFMRI‐M (r s = 0.68, P < 0.001), and PDFFDixon (r s = 0.67, P < 0.001), whereas no correlation was found with CAP. MRE and IVIM diffusion and perfusion significantly correlated with disease activity (r s = 0.55, P < 0.001, r s = −0.40, P = 0.016, r s = −0.37, P = 0.027, respectively) and fibrosis (r s = 0.55, P < 0.001, r s = −0.46, P = 0.0051; r s = −0.53, P < 0.001, respectively). MRE and IVIM diffusion had the highest area‐under‐the‐curve for distinction between simple steatosis and NASH (0.79 and 0.73, respectively).Data ConclusionMultiparametric MRI is a promising method for noninvasive, accurate, and sensitive distinction between simple hepatic steatosis and NASH, as well as for the assessment of steatosis and fibrosis severity.Level of Evidence2Technical Efficacy2

Simulation of intravoxel incoherent perfusion signal using a realistic capillary network of a mouse brain.

To simulate the intravoxel incoherent perfusion magnetic resonance magnitude signal from the motion of blood particles in three realistic vascular network graphs from a mouse brain. In three networks generated from the cortex of a mouse scanned by two-photon laser microscopy, blood flow in each vessel was simulated using Poiseuille's law. The trajectories, flow speeds and phases acquired by a fixed number of simulated blood particles during a Stejskal-Tanner bipolar pulse gradient scheme were computed. The resulting magnitude signal was obtained by integrating all phases and the pseudo-diffusion coefficient D* was estimated by fitting an exponential signal decay. To better understand the anatomical source of the intravoxel incoherent motion (IVIM) perfusion signal, the above was repeated restricting the simulation to various types of vessel. The characteristics of the three microvascular networks were respectively vessel lengths (mean ± std. dev.) 67.2 ± 53.6 μm, 59.8 ± 46.2 μm and 64.5 ± 50.9 μm, diameters 6.0 ± 3.5 μm, 5.7 ± 3.6 μm and 6.1 ± 3.7 μm and simulated blood velocity 0.9 ± 1.7 μm/ms, 1.4 ± 2.5 μm/ms and 0.7 ± 2.1 μm/ms. Exponential fitting of the simulated signal decay as a function of b-value resulted in the following D*-values [10-3 mm2 /s]: 31.7, 40.4 and 33.4. The signal decay for low b-values was the largest in the larger vessels, but the smaller vessels and the capillaries accounted for more of the total volume of the networks. This simulation improves the theoretical understanding of the IVIM perfusion estimation method by directly linking the MR IVIM perfusion signal to an ultra-high resolution measurement of the microvascular network and a realistic blood flow simulation.

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.

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.

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.

Biexponential analysis of intravoxel incoherent motion in calf muscle before and after exercise: Comparisons with arterial spin labeling perfusion and T2

PurposeThis study aimed to clarify exercise-induced changes in intravoxel incoherent motion (IVIM) parameters obtained from diffusion-weighted imaging (DWI) of the calf muscle, as well as the relationships between IVIM parameters, perfusion, and water content in muscle tissue. Materials and methodsThirteen healthy volunteers underwent IVIM-DWI, arterial spin labeling (ASL), and multi-echo spin-echo T2 mapping of the right calf on a 3.0-T magnetic resonance imaging scanner before and after performing dorsiflexion exercise. From the data, we derived the perfusion-related diffusion coefficient (D⁎), perfusion component fraction (F), blood flow parameter (FD⁎), and restricted diffusion coefficient (D) in the tibialis anterior muscle. The muscle blood flow (MBF) and transverse relaxation time (T2) were also calculated from the ASL and multi-echo spin-echo data, respectively. We compared the parameters measured before and after exercise and assessed the relationship of each IVIM-derived perfusion parameter (D⁎, F, and FD⁎) with MBF and each diffusion parameter (D and ADC) or F with T2. ResultsNotably, all these parameters were significantly increased after exercise. Before exercise, the FD⁎ exhibited a significant positive correlation with the MBF, whereas no significant correlation was observed between D⁎ or F and MBF. After exercise, both D⁎ and FD⁎ exhibited significant positive correlations with MBF, whereas F was not significantly correlated with MBF. Additionally, D was significantly correlated with T2 after exercise, but not before exercise. No significant correlations were found between ADC and T2 either before or after exercise. ConclusionsThe IVIM analyses before and after exercise enable the simultaneous evaluation of exercise-induced changes in perfusion and water diffusion in the muscle and increases the body of information on muscle physiology.