Intravoxel Incoherent Motion Metrics Research Articles

Diffusion-sensitized magnetic resonance imaging highlights placental microstructural damage in patients with previous SARS-CoV-2 pregnancy infection

IntroductionSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been a major global health problem since December 2019. This work aimed to investigate whether pregnant women's mild and moderate SARS-CoV-2 infection was associated with microstructural and vascular changes in the placenta observable in vivo by Intravoxel Incoherent Motion (IVIM) at different gestational ages (GA). MethodsThis was a retrospective, nested case-control of pregnant women during the SARS-CoV-2 pandemic (COVID-19 group, n = 14) compared to pre-pandemic healthy controls (n = 19). MRI IVIM protocol at 1.5T was constituted of diffusion-weighted (DW) images with TR/TE = 3100/76 ms and 10 b-values (0,10,30,50,75,100,200,400,700,1000s/mm2). Differences between IVIM parameters D (diffusion), and f (fractional perfusion) quantified in the two groups were evaluated using the ANOVA test with Bonferroni correction and linear correlation between IVIM metrics and GA, COVID-19 duration, the delay time between a positive SARS-CoV-2 test and MRI examination (delay-time exam+) was studied by Pearson-test. ResultsD was significantly higher in the COVID-19 placentas compared to that of the age-matched healthy group (p < 0.04 in fetal and p < 0.007 in maternal site). No significant difference between f values was found in the two groups suggesting no-specific microstructural damage with no perfusion alteration (potentially quantified by f) in mild/moderate SARS-Cov-2 placentas. A significant negative correlation was found between D and GA in the COVID-19 placentas whereas no significant correlation was found in the control placentas reflecting a possible accelerated senescence process due to COVID-19. DiscussionWe report impaired microstructural placental development during pregnancy and the absence of perfusion-IVIM parameter changes that may indicate no perfusion changing through microvessels and microvilli in the placentas of pregnancies with mild/moderate SARS-Cov-2 after reaching negativity.

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.

Value of Intravoxel Incoherent Motion (IVIM) Imaging for Differentiation between Intrahepatic Cholangiocarcinoma and Hepatocellular Carcinoma.

Efficient noninvasive imaging techniques in the differentiation of intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are very important because of their different management and prognosis. Our purpose was to evaluate the difference of parameters extracted from intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) between the two groups and their performance for the differentiation, as well as the significance of perfusion information. IVIM studies (9 b-values) in 41 patients with either ICC or HCC were reviewed retrospectively by two observers. Diffusion coefficient (D), pseudodiffusion coefficient (D∗), perfusion fraction (f), ADC, and the mean percentage of parenchymal enhancement (MPPE) at 30 s after contrast-enhancement were calculated and compared between ICC and HCC. The relationship between D∗, f values, and MPPE was evaluated by Spearman's correlation test. The diagnostic efficacy of all parameters was analyzed by the receiver operating characteristic (ROC) curve. Interobserver and intraobserver agreements were analyzed. The parameters (D and ADC) of ICC were distinctly higher than those of HCC; whereas the parameters (f and MPPE of arterial phase) were distinctly lower (all false discovery rate [FDR]-corrected P < 0.05). The metric D∗ value of ICC was slightly higher than that of HCC (71.44 vs 69.41) with FDR-corrected P > 0.05. Moreover, the value of parameter D was significantly lower than that of ADC (FDR-corrected P < 0.05). The parameters (D and f values) extracted from IVIM showed excellent diagnostic efficiency in the identification, and the diagnostic efficiency of D value was significantly higher than that of the ADC. There were positive correlations between perfusion-related parameters (D∗, f values) and MPPE. Interobserver and intraobserver agreements were excellent or perfect in measurements of all parameters. Parameters derived from IVIM were valuable for distinguishing ICC and HCC. Moreover, the D value showed better diagnostic efficiency for the differential diagnosis than monoexponential fitting-derived ADC value. Meanwhile, the significant correlation between perfusion-related parameters and MPPE demonstrates that specific IVIM metrics may serve as a noninvasive indicator for the vascular perfusion information of ICC and HCC.

IVIM Modeling Shows Increased Perfusion and Free Water in Psychotic Spectrum Disorders Relate to Illness Duration and Cognitive Function

Previous research has shown altered perfusion and free water (FW) in Psychotic Spectrum Disorders (PSD). We applied a three-compartment intravoxel incoherent motion (IVIM) technique that estimated the perfusion fraction (PF), FW, and anisotropic diffusion of tissue (FAt) to detect microvascular and microstructural changes in PSD. We additionally tested whether IVIM metrics vary with the duration from psychosis onset and relate to cognitive function in PSD.

1116 Microstructural & functional changes in the placenta during the COVID-19 pandemic

To study the impact of the COVID-19 pandemic on in vivo microstructural and functional placental development using intra-voxel incoherent motion (IVIM) and blood oxygen level dependent (BOLD) MRI, respectively. This is prospective, observational study of pregnant women with singleton gestations during the COVID-19 pandemic (May 2020-present), compared to pre-pandemic historical controls (July 2014-February 2020). Placental imaging was identical for pandemic and pre-pandemic cohorts: including T2W anatomic images, PGSE sequences for IVIM [TE/TR=53.8/8000ms with 9 b-values (0-900s/mm2)], gradient-echo planar imaging sequences for BOLD imaging (TE/TR=60/2000ms) using a 6 minute maternal hyperoxia design, followed by 6 minutes of normoxia as return to baseline. 28 pregnant women during COVID-19 were included and compared to 100 pre-pandemic healthy controls (IVIM) and 57 pre-pandemic healthy controls (BOLD). The average gestational age (GA) was 28.6±6.0, 29.2±5.8 and 30.1±3.9, respectively. IVIM metrics trended higher for placental diffusion and lower for placental perfusion compared to pre-pandemic controls (Table 1). BOLD functional MRI revealed significantly lower placental oxygenation during minutes 2-6 of maternal hyperoxia and during minutes 1-3 of return to resting state (post hyperoxia) compared to pre-pandemic controls (Figure 1). Respiratory pandemics have been associated with altered intrauterine programing that can result in fetal onset of adult diseases. While the mechanisms are unclear, the placenta is a critical organ that mediates maternal well-being with fetal development. We report altered microstructural and functional placental development during the COVID-19 pandemic in COVID-19 negative women. Neurodevelopmental assessments of these infants are ongoing to determine the short- and long-term effects of these changes.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Intravoxel incoherent motion (IVIM) modeling of diffusion MRI during chemoradiation predicts therapeutic response in IDH wildtype glioblastoma

BackgroundPrediction of early progression in glioblastoma may provide an opportunity to personalize treatment. Simplified intravoxel incoherent motion (IVIM) MRI offers quantitative estimates of diffusion and perfusion metrics. We investigated whether these metrics, during chemoradiation, could predict treatment outcome. Methods38 patients with newly diagnosed IDH-wildtype glioblastoma undergoing 6-week/30-fraction chemoradiation had standardized post-operative MRIs at baseline (radiation planning), and at the 10th and 20th fractions. Non-overlapping T1-enhancing (T1C) and non-enhancing T2-FLAIR hyperintense regions were independently segmented. Apparent diffusion coefficient (ADCT1C, ADCT2-FLAIR) and perfusion fraction (fT1C, fT2-FLAIR) maps were generated with simplified IVIM modelling. Parameters associated with progression before or after 6.9 months (early vs late progression, respectively), overall survival (OS) and progression-free survival (PFS) were investigated. ResultsHigher ADCT2-FLAIR at baseline [Odds Ratio (OR) = 1.06, 95% CI 1.01–1.15, p = 0.025], lower fT2-FLAIR at fraction 10 (OR = 2.11, 95% CI 1.04–4.27, p = 0.018), and lack of increase in ADCT2-FLAIR at fraction 20 compared to baseline (OR = 1.12, 95% CI 1.02–1.22, p = 0.02) were associated with early progression. Combining ADCT2-FLAIR at baseline, fT2-FLAIR at fraction 10, ECOG and MGMT promoter methylation status significantly improved AUC to 90.3% compared to a model with only ECOG and MGMT promoter methylation status (p = 0.001). Using multivariable analysis, neither IVIM metrics were associated with OS but higher fT2-FLAIR at fraction 10 (HR = 0.72, 95% CI 0.56–0.95, p = 0.018) was associated with longer PFS. ConclusionADCT2-FLAIR at baseline, its lack of increase from baseline to fraction 20, or fT2-FLAIR at fraction 10 significantly predicted early progression. fT2-FLAIR at fraction 10 was associated with PFS.

Isotropically weighted intravoxel incoherent motion brain imaging at 7T

Perfusion magnetic resonance imaging (MRI) is a promising non-invasive technique providing insights regarding the brain's microvascular architecture in vivo. The scalar perfusion metrics can be used for quantitative diagnostics of various brain abnormalities, in particular, in the stroke cases and tumours. However, conventional MRI-based perfusion approaches such as dynamic contrast-enhanced perfusion imaging or arterial spin labelling have a few weaknesses, for instance, contrast agent deposition, low signal-to-noise ratio, limited temporal and spatial resolution, and specific absorption rate constraints. As an alternative, the intravoxel incoherent motion (IVIM) approach exploits an extension of diffusion MRI in order to estimate perfusion parameters in the human brain. Application of IVIM imaging at ultra-high field MRI might employ the advantage of a higher signal-to-noise ratio, and thereby the use of higher spatial and temporal resolutions.In the present work, we demonstrate an application of recently developed isotropic diffusion weighted sequences to the evaluation of IVIM parameters at an ultra-high 7T field. The used sequence exhibits high immunity to image degrading factors and allows one to acquire the data in a fast and efficient way. Utilising the bi-exponential fitting model of the signal attenuation, we performed an extensive analysis of the IVIM scalar metrics obtained by a isotropic diffusion weighted sequence in vivo and compared results with a conventional pulsed gradient sequence at 7T. In order to evaluate a possible metric bias originating from blood flows, we additionally used a truncated b-value protocol (b-values from 100 to 200 s/mm2 with the step 20 s/mm2) accompanied to the full range (b-values from 0 to 200 s/mm2). The IVIM scalar metrics have been assessed and analysed together with a large and middle vessel density atlas of the human brain. We found that the diffusion coefficients and perfusion fractions of the voxels consisting of large and middle vessels have higher values in contrast to other tissues. Additionally, we did not find a strong dependence of the IVIM metrics on the density values of the vessel atlas. Perspectives and limitations of the developed isotropic diffusion weighted perfusion are presented and discussed.

Evaluating histologic differentiation of hepatitis B virus-related hepatocellular carcinoma using intravoxel incoherent motion and AFP levels alone and in combination.

To evaluate histologic differentiation of hepatitis B virus (HBV)-related hepatocellular carcinomas (HCCs) using apparent diffusion coefficient (ADC) and intravoxel incoherent motion (IVIM)-derived metrics and to compare findings with alpha-fetoprotein (AFP) levels alone and in combination. One hundred and six chronic HBV-related HCC patients who underwent IVIM diffusion-weighted magnetic resonance imaging with eleven b values were enrolled. Mean ADC, diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) values were determined for all detected lesions. The metrics and AFP levels of different histologically differentiated groups were compared. Spearman's rank correlation was used to assess the statistical dependence among the histologically differentiated HCCs. Receiver operating characteristic (ROC) analysis was performed to evaluate diagnostic performance of these metrics and AFP levels alone and in combination. ADC, D, and f values and AFP levels were significantly different among well-, moderately, and poorly differentiated HCCs. The four metrics were significantly correlated with histologic differentiation. The area under the ROC curve (AUC-ROC) of ADC, D, f, and AFP for diagnosing well-differentiated HCCs was 0.903, 0.84, 0.782, and 0.806, respectively, and the AUC-ROC of above metrics for diagnosing poorly differentiated HCCs was 0.787, 0.726, 0.624, and 0.633, respectively. The combination of ADC and AFP provided an AUC-ROC of 0.945 for well-differentiated HCC. However, this did not provide better performance for diagnosing poorly differentiated HCC. ADC, IVIM metrics, and AFP levels may be useful for evaluating histologic differentiation of HBV-related HCCs, and the combination of ADC and AFP provides better diagnostic performance for well-differentiated HCC.

Intravoxel incoherent motion (IVIM) histogram biomarkers for prediction of neoadjuvant treatment response in breast cancer patients

ObjectiveTo examine the prognostic capabilities of intravoxel incoherent motion (IVIM) metrics and their ability to predict response to neoadjuvant treatment (NAT). Additionally, to observe changes in IVIM metrics between pre- and post-treatment MRI. MethodsThis IRB-approved, HIPAA-compliant retrospective study observed 31 breast cancer patients (32 lesions). Patients underwent standard bilateral breast MRI along with diffusion-weighted imaging before and after NAT. Six patients underwent an additional IVIM-MRI scan 12–14 weeks after initial scan and 2 cycles of treatment. In addition to apparent diffusion coefficients (ADC) from monoexponential decay, IVIM mean values (tissue diffusivity Dt, perfusion fraction fp, and pseudodiffusivity Dp) and histogram metrics were derived using a biexponential model. An additional filter identified voxels of highly vascular tumor tissue (VTT), excluding necrotic or normal tissue. Clinical data include histology of biopsy and clinical response to treatment through RECIST assessment. Comparisons of treatment response were made using Wilcoxon rank-sum tests. ResultsAverage, kurtosis, and skewness of pseudodiffusion Dp significantly differentiated RECIST responders from nonresponders. ADC and Dt values generally increased (∼70%) and VTT% values generally decreased (∼20%) post-treatment. ConclusionDp metrics showed prognostic capabilities; slow and heterogeneous pseudodiffusion offer poor prognosis. Baseline ADC/Dt parameters were not significant predictors of response. This work suggests that IVIM mean values and heterogeneity metrics may have prognostic value in the setting of breast cancer NAT.

Evaluation and Minimization of the Pseudohepatic Anisotropy Artifact in Liver Intravoxel Incoherent Motion.

The aim of this study was to evaluate the effect of the pseudohepatic anisotropy artifact on liver intravoxel incoherent motion (IVIM) metrics and whether the use of multiple gradient directions in the IVIM acquisition minimizes the artifact. Multiple breath-holding and forced shallow free-breathing IVIM scans were performed on 8 healthy volunteers using 1 and 6 gradient directions. Cluster analysis was carried out to separate motion-contaminated parenchyma from liver parenchyma and vessels. Nonlinear motion analysis was also performed to look for a possible link between IVIM metrics and nonlinear liver motion. On the basis of the resulted clusters, motion-contaminated parenchyma is often noted in the left liver lobe, where the prominent pseudohepatic artifact has previously been identified. A significant reduction in outliers was obtained with the acquisition of 6 noncoplanar gradient directions and when using forced shallow free-breathing. The pseudohepatic anisotropy artifact can be minimized when using multiple diffusion-encoding gradient directions and forced free-breathing during IVIM acquisition.

Correlation between Intravoxel Incoherent Motion Magnetic Resonance Imaging Derived Metrics and Serum Soluble CD40 Ligand Level in an Embolic Canine Stroke Model.

ObjectiveTo determine the relationship between intravoxel incoherent motion (IVIM) imaging derived quantitative metrics and serum soluble CD40 ligand (sCD40L) level in an embolic canine stroke model.Materials and MethodsA middle cerebral artery occlusion model was established in 24 beagle dogs. Experimental dogs were divided into low- and high-sCD40L group according to serum sCD40L level at 4.5 hours after establishing the model. IVIM imaging was scanned at 4.5 hours after model establishment using 10 b values ranging from 0 to 900 s/mm2. Quantitative metrics diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) of ischemic lesions were calculated. Quantitative metrics of ischemic lesions were normalized by contralateral hemisphere using the following formula: normalized D = Dstroke / Dcontralateral. Differences in IVIM metrics between the low- and high-sCD40L groups were compared using t test. Pearson's correlation analyses were performed to determine the relationship between IVIM metrics and serum sCD40L level.ResultsThe high-sCD40L group showed significantly lower f and normalized f values than the low-sCD40L group (f, p < 0.001; normalized f, p < 0.001). There was no significant difference in D*, normalized D*, D, or normalized D value between the two groups (All p > 0.05). Both f and normalized f values were negatively correlated with serum sCD40L level (f, r = −0.789, p < 0.001; normalized f, r = −0.823, p < 0.001). However, serum sCD40L level had no significant correlation with D*, normalized D*, D, or normalized D (All p > 0.05).ConclusionThe f value derived from IVIM imaging was negatively correlated with serum sCD40L level. f value might serve as a potential imaging biomarker to assess the formation of microvascular thrombosis in hyperacute period of ischemic stroke.

Intravoxel incoherent motion (IVIM)-derived parameters in diffusion-weighted MRI: Associations with prognostic factors in invasive ductal carcinoma.

To investigate relationships between intravoxel incoherent motion (IVIM) metrics of invasive ductal carcinoma of the breast and prognostic factors. This retrospective study included a total of 82 masses from 72 patients who underwent 3T breast magnetic resonance imaging (MRI) and diffusion-weighted imaging. IVIM metrics of tissue diffusivity (Dslow ), pseudodiffusivity (Dfast ), and perfusion fraction (Dpf ) were measured using histogram analysis for whole lesion volumes. We evaluated relationships between IVIM metrics and prognostic factors or subtypes of invasive ductal carcinoma. The Dslow 50th , 75th , and 90th percentile metrics were reduced in the estrogen receptor (ER)-positive group compared with the ER-negative group (individually, P = 0.044, 0.024, 0.045). Additionally, the Dslow 75th percentile value was a significant differentiator of histologic grade, tumor subtype, and Ki-67 grouping (individually, P = 0.024, 0.049, 0.016). The Dpf mean, 75th , 90th percentile, skewness, and kurtosis metrics were correlated with the size of ductal carcinoma in situ (DCIS) component (individually, P = 0.034, 0.032, 0.027, 0.013, 0.013). The Dslow metrics differentiated between ER-positive and -negative groups, and the Dpf metrics were associated with the size of the DCIS component. 4 J. MAGN. RESON. IMAGING 2017;45:1394-1406.

Voxelwise analysis of simultaneously acquired and spatially correlated 18 F-fluorodeoxyglucose (FDG)-PET and intravoxel incoherent motion metrics in breast cancer.

Diffusion-weighted imaging (DWI) and 18 F-fluorodeoxyglucose-positron emission tomography (18 F-FDG-PET) independently correlate with malignancy in breast cancer, but the relationship between their structural and metabolic metrics is not completely understood. This study spatially correlates diffusion, perfusion, and glucose avidity in breast cancer with simultaneous PET/MR imaging and compares correlations with clinical prognostics. In this Health Insurance Portability and Accountability Act-compliant prospective study, with written informed consent and approval of the institutional review board and using simultaneously acquired FDG-PET and DWI, tissue diffusion (Dt ), and perfusion fraction (fp ) from intravoxel incoherent motion (IVIM) analysis were registered to FDG-PET within 14 locally advanced breast cancers. Lesions were analyzed using 2D histograms and correlation coefficients between Dt , fp , and standardized uptake value (SUV). Correlations were compared with prognostics from biopsy, metastatic burden from whole-body PET, and treatment history. SUV||Dt correlation coefficient significantly distinguished treated (0.11 ± 0.24) from nontreated (-0.33 ± 0.26) patients (P = 0.005). SUV||fp correlations were on average negative for the whole cohort (-0.17 ± 0.13). Simultaneously acquired and registered FDG-PET/DWI allowed quantifiable descriptions of breast cancer microenvironments that may provide a framework for monitoring and predicting response to treatment. Magn Reson Med 78:1147-1156, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Intravoxel Incoherent Motion Metrics as Potential Biomarkers for Survival in Glioblastoma.

ObjectiveIntravoxel incoherent motion (IVIM) is an MRI technique with potential applications in measuring brain tumor perfusion, but its clinical impact remains to be determined. We assessed the usefulness of IVIM-metrics in predicting survival in newly diagnosed glioblastoma.MethodsFifteen patients with glioblastoma underwent MRI including spin-echo echo-planar DWI using 13 b-values ranging from 0 to 1000 s/mm2. Parametric maps for diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) were generated for contrast-enhancing regions (CER) and non-enhancing regions (NCER). Regions of interest were manually drawn in regions of maximum f and on the corresponding dynamic susceptibility contrast images. Prognostic factors were evaluated by Kaplan-Meier survival and Cox proportional hazards analyses.ResultsWe found that fCER and D*CER correlated with rCBFCER. The best cutoffs for 6-month survival were fCER>9.86% and D*CER>21.712 x10−3mm2/s (100% sensitivity, 71.4% specificity, 100% and 80% positive predictive values, and 80% and 100% negative predictive values; AUC:0.893 and 0.857, respectively). Treatment yielded the highest hazard ratio (5.484; 95% CI: 1.162–25.88; AUC: 0.723; P = 0.031); fCER combined with treatment predicted survival with 100% accuracy.ConclusionsThe IVIM-metrics fCER and D*CER are promising biomarkers of 6-month survival in newly diagnosed glioblastoma.

Early Assessment of Colorectal Cancer Patients with Liver Metastases Treated with Antiangiogenic Drugs: The Role of Intravoxel Incoherent Motion in Diffusion-Weighted Imaging.

PurposeTo assess the feasibility and effectiveness of quantitative intravoxel incoherent motion (IVIM) of Diffusion-weighted imaging (DWI) in the assessment of liver metastases treated with targeted chemotherapy agents.Methods12 patients with unresectable liver metastases from colorectal cancer were enrolled and received neoadjuvant FOLFIRI (5-fluorouracil, leucovorin, irinotecan) plus bevacizumab therapy. DWI was performed for 36 metastases at baseline and after 14 days from starting the treatment. In addition to the basic IVIM metrics, the product between pseudo-diffusivity and perfusion fraction was considered as a descriptor roughly analogous to the flow. Median diffusion parameters of Region of Interest (ROI) were used as representative values for each lesion. Normalized parameters in comparison with the median value of spleen were also collected. The percentual change of the diffusion parameters was calculated. The response to chemotherapy was evaluated according the Response Evaluation Criteria in Solid Tumors (RECIST) as calculated on whole-body CT scan obtained three months after treatment. Mann Whitney test and Receiver operating characteristic (ROC) analysis were performed.Results24 lesions were categorized as responding and 12 as not responding. There was no statistically significant difference among absolute and normalized diffusion parameters between the pretreatment and the post-treatment findings. Instead, the perfusion fraction (fp) values showed a statistical difference between responder and non-responder lesions: sensitivity and specificity of fp variation was 62% and 93%, respectively.ConclusionsIVIM parameters represent a valuable tool in the evaluation of the anti-angiogenic therapy in patients with liver metastases from colorectal cancer. A percentage change of fp represents the most effective DWI marker in the assessment of tumor response.

Intravoxel incoherent motion imaging kinetics during chemoradiotherapy for human papillomavirus-associated squamous cell carcinoma of the oropharynx: preliminary results from a prospective pilot study.

This study aims to identify the temporal kinetics of intravoxel incoherent motion (IVIM) MRI in patients with human papillomavirus-associated (HPV+) oropharyngeal squamous cell carcinoma. Patients were enrolled under an Institutional Review Board (IRB)-approved protocol as part of an ongoing prospective clinical trial. All patients underwent two MRI studies: a baseline scan before chemoradiotherapy and a mid-treatment scan 3-4 weeks after treatment initiation. Parametric maps representing pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f) and apparent diffusion coefficient (ADC) were generated. The Mann-Whitney U-test was used to assess the temporal variation of IVIM metrics. Bayesian quadratic discriminant analysis (QDA) was used to evaluate the extent to which mid-treatment changes in IVIM metrics could be combined to predict sites that would achieve complete response (CR) in multivariate analysis. Thirty-one patients were included in the final analysis with 59 lesions. Pretreatment ADC and D values of the CR lesions (n = 19) were significantly lower than those of non-CR lesions (n = 33). Mid-treatment ADC, D and f values were significantly higher (p < 0.0001) than pretreatment values for all lesions. Each increase in normalized ΔADC of size 0.1 yielded a 1.45-fold increase in the odds of CR (p < 0.0003), each increase in normalized ΔD of size 0.1 yielded a 1.53-fold increase in the odds of CR (p < 0.0002), and each unit increase in Δf yielded a 2.29-fold increase in the odds of CR (p < 0.02). Combined ΔD and ΔADC were integrated into a multivariate prediction model and attained an AUC of 0.87 (95% confidence interval: 0.79, 0.96), as well as a sensitivity of 0.63, specificity of 0.85 and accuracy of 0.78, under leave-one-out cross-validation. In conclusion, IVIM is feasible and potentially useful in the prediction and assessment of the early response of HPV+ oropharyngeal squamous cell carcinoma to chemoradiotherapy.

Intravoxel incoherent motion diffusion imaging of the liver: Optimal b-value subsampling and impact on parameter precision and reproducibility

PurposeTo increase diffusion sampling efficiency in intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) of the liver by reducing the number of diffusion weightings (b-values). Materials and methodsIn this IRB approved HIPAA compliant prospective study, 53 subjects (M/F 38/15, mean age 52±13 y) underwent IVIM DWI at 1.5T using 16 b-values (0–800s/mm2), with 14 subjects having repeat exams to assess IVIM parameter reproducibility. A biexponential diffusion model was used to quantify IVIM hepatic parameters (PF: perfusion fraction, D: true diffusion and D*: pseudo diffusion). All possible subsets of the 16 b-values were probed, with number of b values ranging from 4 to 15, and corresponding parameters were quantified for each subset. For each b-value subset, global parameter estimation error was computed against the parameters obtained with all 16 b-values and the subsets providing the lowest error were selected. Interscan estimation error was also evaluated between repeat exams to assess reproducibility of the IVIM technique in the liver. The optimal b-values distribution was selected such that the number of b-values was minimal while keeping parameter estimation error below interscan reproducibility error. ResultsAs the number of b-values decreased, the estimation error increased for all parameters, reflecting decreased precision of IVIM metrics. Using an optimal set of 4 b-values (0, 15, 150 and 800s/mm2), the errors were 6.5, 22.8 and 66.1% for D, PF and D* respectively. These values lie within the range of test–retest reproducibility for the corresponding parameters, with errors of 12.0, 32.3 and 193.8% for D, PF and D* respectively. ConclusionA set of 4 optimized b-values can be used to estimate IVIM parameters in the liver with significantly shorter acquisition time (up to 75%), without substantial degradation of IVIM parameter precision and reproducibility compared to the 16 b-value acquisition used as the reference.

Hepatocellular carcinoma: Short‐term reproducibility of apparent diffusion coefficient and intravoxel incoherent motion parameters at 3.0T

To evaluate short-term test-retest and interobserver reproducibility of IVIM (intravoxel incoherent motion) diffusion parameters and ADC (apparent diffusion coefficient) of hepatocellular carcinoma (HCC) and liver parenchyma at 3.0T. In this prospective Institutional Review Board (IRB)-approved study, 11 patients were scanned twice using a free-breathing single-shot echo-planar-imaging, diffusion-weighted imaging (DWI) sequence using 4 b values (b = 0, 50, 500, 1000 s/mm(2)) and IVIM DWI using 16 b values (0-800 s/mm(2)) at 3.0T. IVIM parameters (D: true diffusion coefficient, D*: pseudodiffusion coefficient, PF: perfusion fraction) and ADC (using 4 b and 16 b) were calculated. Short-term test-retest and interobserver reproducibility of IVIM parameters and ADC were assessed by measuring correlation coefficient, coefficient of variation (CV), and Bland-Altman limits of agreements (BA-LA). Fifteen HCCs were assessed in 10 patients. Reproducibility of IVIM metrics in HCC was poor for D* and PF (mean CV 60.6% and 37.3%, BA-LA: -161.6% to 135.3% and -66.2% to 101.0%, for D* and PF, respectively), good for D and ADC (CV 19.7% and <16%, BA-LA -57.4% to 36.3% and -38.2 to 34.1%, for D and ADC, respectively). Interobserver reproducibility was on the same order of test-retest reproducibility except for PF in HCC. Reproducibility of diffusion parameters was better in liver parenchyma compared to HCC. Poor reproducibility of D*/PF and good reproducibility for D/ADC were observed in HCC and liver parenchyma. These findings may have implications for trials using DWI in HCC.

Interstitial fluid pressure correlates with intravoxel incoherent motion imaging metrics in a mouse mammary carcinoma model

The effective delivery of a therapeutic drug to the core of a tumor is often impeded by physiological barriers, such as the interstitial fluid pressure (IFP). There are a number of therapies that can decrease IFP and induce tumor vascular normalization. However, a lack of a noninvasive means to measure IFP hinders the utilization of such a window of opportunity for the maximization of the treatment response. Thus, the purpose of this study was to investigate the feasibility of using intravoxel incoherent motion (IVIM) diffusion parameters as noninvasive imaging biomarkers for IFP. Mice bearing the 4T1 mammary carcinoma model were studied using diffusion-weighted imaging (DWI), immediately followed by wick-in-needle IFP measurement. Voxelwise analysis was conducted with a conventional monoexponential diffusion model, as well as a biexponential model taking IVIM into account. There was no significant correlation of IFP with either the median apparent diffusion coefficient from the monoexponential model (r = 0.11, p = 0.78) or the median tissue diffusivity from the biexponential model (r = 0.30, p = 0.44). However, IFP was correlated with the median pseudo-diffusivity (D(p)) of apparent vascular voxels (r = 0.76, p = 0.02) and with the median product of the perfusion fraction and pseudo-diffusivity (f(p)D(p)) of apparent vascular voxels (r = 0.77, p = 0.02). Although the effect of IVIM in tumors has been reported previously, to our knowledge, this study represents the first direct comparison of IVIM metrics with IFP, with the results supporting the feasibility of the use of IVIM DWI metrics as noninvasive biomarkers for tumor IFP.