Application of Intravoxel Incoherent Motion in Clinical Liver Imaging: A Literature Review.

Intravoxel incoherent motion (IVIM) modeling is a widely used double-exponential model for describing diffusion-weighted imaging (DWI) signal, with a slow component related to pure molecular diffusion and a fast component associated with microcirculatory perfusion, which compensates for the limitations of traditional DWI. IVIM is a noninvasive technique for obtaining liver pathological information and characterizing liver lesions, and has potential applications in the initial diagnosis and treatment monitoring of liver diseases. Recent studies have demonstrated that IVIM-derived parameters are useful for evaluating liver lesions, including nonalcoholic fatty liver disease (NAFLD), liver fibrosis and liver tumors. However, the results are not stable. Therefore, it is necessary to summarize the current applications of IVIM in liver disease research, identify existing shortcomings, and point out the future development direction. In this review, we searched for studies related to hepatic IVIM-DWI applications over the past two decades in the PubMed database. We first introduce the fundamental principles and influential factors of IVIM, and then discuss its application in NAFLD, liver fibrosis, and focal hepatic lesions. It has been found that IVIM is still unstable in ensuring the robustness and reproducibility of measurements in the assessment of liver fibrosis grade and liver tumors differentiation, due to inconsistent and substantial overlap in the range of IVIM-derived parameters for different fibrotic stages. In the end, the future direction of IVIM-DWI in the assessment of liver diseases is discussed, emphasizing the need for further research on the stability of IVIM-derived parameters, particularly perfusion-related parameters, in order to promote the clinical practice of IVIM-DWI. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 3.

Assessment of hepatic sinusoidal obstruction syndrome with intravoxel incoherent motion diffusion-weighted imaging: An experimental study in a rat model.

BACKGROUND: Intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) parameters may reflect perfusion and diffusion changes in hepatic sinusoidal obstruction syndrome (SOS). PURPOSE: To investigate the feasibility of IVIM-DWI in the noninvasive assessment of hepatic SOS in an experimental rat model. STUDY TYPE: Animal study. POPULATION/SUBJECTS: Forty-four rats were administered different doses (90 or 160 mg/kg) of monocrotaline by gavage either 48 or 72 hours before MRI to induce different degrees of hepatic SOS, and another 10 rats served as controls. FIELD STRENGTH/SEQUENCE: 3T scanner, IVIM-DWI using nine b values (0-800 sec/mm2 ). ASSESSMENT: Histologically, rats were classified as having none (n = 10), mild (n = 8), moderate (n = 19), or severe SOS (n = 17). The apparent diffusion coefficient (ADC) and IVIM-derived parameters (D: true diffusion coefficient, D*: pseudo-diffusion coefficient, and f: perfusion fraction) of the liver parenchyma were measured. STATISTICAL TESTS: IVIM-DWI parameters were compared according to histologic grades of SOS (none, mild, moderate, and severe), and receiver operating characteristic (ROC) curve analysis was performed to determine the diagnostic accuracy. RESULTS: ADC, D, and f of the liver parenchyma were significantly different according to SOS severity groups (Ps < 0.01) and significantly decreased as SOS severity increased (rho = -0.323, -0.313, and -0.700; P = 0.017, 0.021, and <0.001, respectively). Means of f in none, mild, moderate, and severe SOS were 17.2%, 13.3%, 12.3%, and 11.1%, respectively. Among ADC and IVIM-derived parameters, f provided the highest area under the ROC curves for detecting ≥mild, ≥moderate, and severe SOS (0.991, 0.890, and 0.803, respectively). DATA CONCLUSION: IVIM-DWI may be useful in the diagnosis and severity assessment of hepatic SOS. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:81-89.

Multiparametric MRI Evaluation of Liposomal Prostaglandins E1 Intervention on Hepatic Warm Ischemia-Reperfusion Injury in Rabbits.

BACKGROUND: Liposomal prostaglandin E1 (Lipo-PGE1) treatment should protect against hepatic warm ischemia-reperfusion injury (WIRI). Improved methods are needed for the noninvasive evaluation of hepatic responses to prophylactic Lipo-PGE1 pretreatment approaches. PURPOSE: To demonstrate that multiparametric MRI measurements permit noninvasive differentiation of Lipo-PGE1 treatment outcomes in a hepatic WIRI animal model. STUDY TYPE: Animal study. ANIMAL MODEL: Seventy rabbits were randomly divided into a sham-operated group (A0), warm ischemia groups experiencing increasing periods of ischemia (A1-A3), and corresponding intervention groups (I1-I3) (n = 10 for each group). FIELD STRENGTH/SEQUENCE: Imaging was performed at 3T using a multiecho gradient echo (GRE) sequence (repetition time / echo time [TR/TE], 75/2.57-24.25 msec) for R2* blood oxygenation level-dependent (BOLD) measurements, free-breathing single-shot echo-planar imaging (ss-EPI) sequence with two b-values (0 and 500 s/mm2 ) in 12 diffusion directions for diffusion tensor imaging (DTI), and a free-breathing ss-EPI sequence with eight b-values (0 to 800 s/mm2 ) for intravoxel incoherent motion (IVIM) measurements. ASSESSMENT: The BOLD-derived parameter (R2*), DTI-derived parameters (ADC, FA), and IVIM-derived parameters (Dslow, Dfast, and PF) were calculated for comparisons between treatment groups and correlation to ALT, AST, and LDH levels. STATISTICAL TESTS: One-way analysis of variance (ANOVA), independent sample t-test, Spearman correlation, and receiver operating characteristic (ROC) analysis were performed. RESULTS: Histopathology confirmed the validity of the WIRI model and the efficacy of intervention with clear structure and morphology differences between the different ischemia times and between the Lipo-PGE1 treatment and control groups. Prolonged warm ischemia times resulted in higher R2* and FA values and gradually lower ADC, Dslow, Dfast, and PF values (all P < 0.05). The R2* and FA values were lower, and the ADC, Dslow, Dfast, and PF values were higher in the Lipo-PGE1 intervention groups compared with those in the warm ischemia group for each paired time. However, none of the parameters reached the levels of the A0 group (all P < 0.05). As the warm ischemia time increased, additional parameters demonstrated significant differences between warm ischemia time groups and corresponding intervention groups. At the shortest (30 min), middle (40 min), and longest (60 min) ischemia times, three, four, and five parameters were significantly different between the WIRI and intervention groups, respectively (all P < 0.05). ADC, Dslow, Dfast, and PF values were negatively correlated, while R2* and FA values were positively correlated with serum ALT (|r| = 0.312-0.606) and AST (|r| = 0.432-0.602) (all P < 0.05). ADC and Dfast values showed negative correlations, and R2* showed positive correlations with serum LDH (|r| = 0.323-0.542, all P < 0.05). ROC analysis showed that DTI yielded the strongest diagnostic performance for evaluating the improvement of WIRI. DATA CONCLUSION: Multiparametric MRI can serve as a noninvasive radiologic evaluation for monitoring the protective impact of Lipo-PGE1 therapy on hepatic WIRI. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;52:217-228.

Intravoxel Incoherent Motion and Arterial Spin Labeling MRI Analysis of Reversible Unilateral Ureteral Obstruction in Rats.

BACKGROUND: Renal fibrosis is a common consequence of chronic kidney disease (CKD) and is the mechanism by which various forms of CKD progress to endstage renal failure. Accurate assessment of renal fibrosis is important for treatment. PURPOSE: To measure longitudinal changes of intravoxel incoherent motion (IVIM) and arterial spin labeling (ASL) before and after reversible unilateral ureteral obstruction in an animal model. STUDY TYPE: Self-controlled animal study. ANIMAL MODEL: Surgical obstruction of the ureters was performed and then removed after 5 days. Rats were scanned on Days 0, 1, 3, and 5 after creating the obstruction and on Days 4, 7, and 12 after releasing the obstruction. FIELD STRENGTH/SEQUENCE: 3.0T/IVIM/ASL. ASSESSMENT: The apparent diffusion coefficient (ADC), pure molecular diffusion (D), perfusion fraction (f), pseudodiffusion (D*), and renal blood flow (RBF) obtained from the ASL were measured. STATISTICAL TESTS: Using SPSS v. 20.0 software, P < 0.05 were considered statistically significant. The data from each timepoint were compared using one-way analysis of variance and correlation analysis was applied to various parameters. RESULTS: The postobstruction kidneys showed renal tubule swelling and increased collagen fiber content. Renal tubule swelling was relieved after reversing the obstruction, but Masson staining and cell density analysis revealed progressive changes that were primarily localized to the medulla. In general, ADC, D, f, D*, and RBF decreased with time during the 5 days of obstruction, and increased after release of the obstruction. ADC positively correlated with D, f, D*, and RBF (r = 0.415, r = 0.634, r = 0.465 r = 0.586, P < 0.001, respectively) in the cortex in this study. Also, ADC showed a positive correlation with D, f, and D* (r = 0.724, r = 0.749, r = 0.151, P < 0.001, respectively) in the medulla. DATA CONCLUSION: Kidney perfusion was the major factor affecting ADC. Functional imaging may be useful for following progression of CKD. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:288-296.

Dependence of intravoxel incoherent motion diffusion MR threshold b-value selection for separating perfusion and diffusion compartments and liver fibrosis diagnostic performance.

BACKGROUND: Intravoxel incoherent motion (IVIM) tissue parameters depend on the threshold b-value. PURPOSE: To explore how threshold b-value impacts PF ( f), Dslow ( D), and Dfast ( D*) values and their performance for liver fibrosis detection. MATERIAL AND METHODS: Fifteen healthy volunteers and 33 hepatitis B patients were included. With a 1.5-T magnetic resonance (MR) scanner and respiration gating, IVIM data were acquired with ten b-values of 10, 20, 40, 60, 80, 100, 150, 200, 400, and 800 s/mm2. Signal measurement was performed on the right liver. Segmented-unconstrained analysis was used to compute IVIM parameters and six threshold b-values in the range of 40-200 s/mm2 were compared. PF, Dslow, and Dfast values were placed along the x-axis, y-axis, and z-axis, and a plane was defined to separate volunteers from patients. RESULTS: Higher threshold b-values were associated with higher PF measurement; while lower threshold b-values led to higher Dslow and Dfast measurements. The dependence of PF, Dslow, and Dfast on threshold b-value differed between healthy livers and fibrotic livers; with the healthy livers showing a higher dependence. Threshold b-value = 60 s/mm2 showed the largest mean distance between healthy liver datapoints vs. fibrotic liver datapoints, and a classification and regression tree showed that a combination of PF (PF < 9.5%), Dslow (Dslow < 1.239 × 10-3 mm2/s), and Dfast (Dfast < 20.85 × 10-3 mm2/s) differentiated healthy individuals and all individual fibrotic livers with an area under the curve of logistic regression (AUC) of 1. CONCLUSION: For segmented-unconstrained analysis, the selection of threshold b-value = 60 s/mm2 improves IVIM differentiation between healthy livers and fibrotic livers.

Rapid measurement of intravoxel incoherent motion (IVIM) derived perfusion fraction for clinical magnetic resonance imaging.

OBJECTIVE: This study aimed to investigate the reliability of intravoxel incoherent motion (IVIM) model derived parameters D and f and their dependence on b value distributions with a rapid three b value acquisition protocol. MATERIALS AND METHODS: Diffusion models for brain, kidney, and liver were assessed for bias, error, and reproducibility for the estimated IVIM parameters using b values 0 and 1000, and a b value between 200 and 900, at signal-to-noise ratios (SNR) 40, 55, and 80. Relative errors were used to estimate optimal b value distributions for each tissue scenario. Sixteen volunteers underwent brain DW-MRI, for which bias and coefficient of variation were determined in the grey matter. RESULTS: Bias had a large influence in the estimation of D and f for the low-perfused brain model, particularly at lower b values, with the same trends being confirmed by in vivo imaging. Significant differences were demonstrated in vivo for estimation of D (P = 0.029) and f (P < 0.001) with [300,1000] and [500,1000] distributions. The effect of bias was considerably lower for the high-perfused models. The optimal b value distributions were estimated to be brain500,1000, kidney300,1000, and liver200,1000. CONCLUSION: IVIM parameters can be estimated using a rapid DW-MRI protocol, where the optimal b value distribution depends on tissue characteristics and compromise between bias and variability.

[Capillary Blood Flow of Muscle Before and After the Exercise Used by Intravoxel Incoherent Motion].

Capillaries are the most basic and important blood vessel of the circulatory systems. The evaluation of the blood flow may contribute to many studies in future. We evaluated the capillary blood flow change of lower limb muscle over time before and after the exercise used by magnetic resonance imaging-intravoxel incoherent motion (MRI-IVIM) obtained perfusion information. Furthermore, we examined an association between the muscle pain after the exercise and the diffusion weighted image (DWI) indexes. DWI was imaged using multi-b values for a thigh and calf muscles. MRI was performed just after an exercise test, 3, 6, and 24 hours later, and the IVIM index and diffusion index were calculated. Furthermore, we interviewed the degree of the muscle ache 24 hours later. As a result, pseudo diffusion coefficient (D*) and f value as IVIM index increased after-exercise as compared with pre-exercise and decreased in 3 hours later. A similar tendency was found in the apparent diffusion coefficient and the diffusion coefficient as diffusion index. Furthermore, all indexes increased in after exercise from before exercise and decreased with time passed and increased again 24 hours later. In conclusion, IVIM could obtain capillary blood flow information, and it was suggested to contribute for sports medicine in future.

Magnetic Resonance Imaging Assessment of Kidney Oxygenation and Perfusion During Sickle Cell Vaso-occlusive Crises.

BACKGROUND: Our understanding of the pathophysiologic processes underlying sickle cell nephropathy remains incomplete. We performed a pilot study to investigate the potential value of magnetic resonance imaging (MRI) for the assessment of kidney oxygenation and detection of potential changes to tissue perfusion and cellular integrity during a vaso-occlusive crisis. STUDY DESIGN: A case-control study. SETTING & PARTICIPANTS: 10 homozygous patients with sickle cell disease (SCD), without kidney disease (based on estimated glomerular filtration rate and albuminuria), underwent renal MRI during a vaso-occlusive crisis episode. The imaging data obtained were compared with those for a second MRI performed at steady state (median, 56 [IQR, 37-72] days after the vaso-occlusive crisis MRI). The control group consisted of 10 apparently healthy individuals. MEASUREMENTS: Deoxyhemoglobin level assessed by R2* value was calculated using the blood oxygen level-dependent technique. The intravoxel incoherent motion diffusion-weighted imaging technique was used to calculate D, D*, and F parameters. RESULTS: Median medullary R2* values on steady-state MRI were significantly higher for patients with SCD than for controls (P=0.01) and did not change significantly during the vaso-occlusive crisis. No significant differences in median cortical R2* values were observed. Both cellular integrity (D) and local perfusion (D* and F) were significantly altered in medullary and cortical areas during vaso-occlusive crises in comparison to steady state in patients with SCD. These parameters did not differ significantly between patients with SCD assessed at steady state and the control group. LIMITATIONS: Small sample size, estimation of glomerular filtration rate according to CKD-EPI creatinine equation without adjustment for race. CONCLUSIONS: Deoxyhemoglobin levels in the medullary area are higher in patients with SCD, during vaso-occlusive crises and at steady state, than in controls. Alterations to the tissue perfusion and cellular integrity of renal parenchyma are a common finding during vaso-occlusive crises that provide additional evidence that a vaso-occlusive crisis may be associated with subclinical kidney injury detectable on MRI.

Intravoxel incoherent motion diffusion-weighted imaging of bone marrow in patients with acute myeloid leukemia: a pilot study of prognostic value.

PURPOSE: To investigate the value of intravoxel incoherent motion (IVIM) parameters in evaluation of prognosis in patients with acute myeloid leukemia (AML) before treatment. MATERIALS AND METHODS: Fifty-three patients before standard chemotherapy underwent MRI scans at 1.5 Tesla using conventional diffusion weighted imaging (DWI) and IVIM (b = 0, 10, 25, 50, 100, 200, 400, 600, 800, 1000, 1200 s/mm2 ) in the sagittal plane covering the lumbar bone marrow. The IVIM parameters (perfusion fraction [f], molecular diffusion coefficient [D], and perfusion-related D [D*] and apparent diffusion coefficient (ADC) were extracted from the bone marrow images. All patients were divided into complete remission (CR) and nonremission (NR) group according to the treatment response. RESULTS: All patients underwent the first remission induction chemotherapy, with 33 patients achieved CR and 20 patients achieved NR. The ADC values were not significant different between the two groups (P = 0.118). However, D value of CR group was significantly higher (P = 0.010), and f value of CR group was significantly lower (P = 0.021) than those of NR group. D* values had no significant differences between the two groups (P = 0.955). The D and f values were significant prognostic factors of AML after controlling for potential confounding factors (age, gender and smoking). Using receiver operator characteristic analysis, the area under the curve of D and f were 0.759 and 0.666, respectively, in evaluating prognosis of AML before treatment. CONCLUSION: There were significant differences in IVIM parameters between CR and NR patients of AML before treatment, and the D and f could play a potential role in prognosticating patients with AML. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:476-482.

Can diffusion-weighted imaging serve as a biomarker of fibrosis in pancreatic adenocarcinoma?

PURPOSE: To assess the relationship between diffusion-weighted imaging (DWI) and intravoxel incoherent motion (IVIM)-derived quantitative parameters (apparent diffusion coefficient [ADC], perfusion fraction [f], Dslow , diffusion coefficient [D], and Dfast , pseudodiffusion coefficient [D*]) and histopathology in pancreatic adenocarcinoma (PAC). MATERIALS AND METHODS: Subjects with suspected surgically resectable PAC were prospectively enrolled in this Health Insurance Portability and Accountability Act (HIPAA)-compliant, Institutional Review Board-approved study. Imaging was performed at 1.5T with a respiratory-triggered echo planar DWI sequence using 10 b values. Two readers drew regions of interest (ROIs) over the tumor and adjacent nontumoral tissue. Monoexponential and biexponential fits were used to derive ADC2b , ADCall , f, D, and D*, which were compared to quantitative histopathology of fibrosis, mean vascular density, and cellularity. Two biexponential IVIM models were investigated and compared: 1) nonlinear least-square fitting based on the Levenberg-Marquardt algorithm, and 2) linear fit using a fixed D* (20 mm2 /s). Statistical analysis included Student's t-test, Pearson correlation (P < 0.05 was considered significant), intraclass correlation, and coefficients of variance. RESULTS: Twenty subjects with PAC were included in the final cohort. Negative correlation between D and fibrosis (Reader 2: r = -0.57 P = 0.01; pooled P = -0.46, P = 0.04) was observed with a trend toward positive correlation between f and fibrosis (r = 0.44, P = 0.05). ADC2b was significantly lower in PAC with dense fibrosis than with loose fibrosis ADC2b (P = 0.03). Inter- and intrareader agreement was excellent for ADC, D, and f. CONCLUSION: In PAC, D negatively correlates with fibrosis, with a trend toward positive correlation with f suggesting both perfusion and diffusion effects contribute to stromal desmoplasia. ADC2b is significantly lower in tumors with dense fibrosis and may serve as a biomarker of fibrosis architecture. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:393-402.

Separation of type and grade in cervical tumours using non-mono-exponential models of diffusion-weighted MRI.

OBJECTIVES: Assessment of empirical diffusion-weighted MRI (DW-MRI) models in cervical tumours to investigate whether fitted parameters distinguish between types and grades of tumours. METHODS: Forty-two patients (24 squamous cell carcinomas, 14 well/moderately differentiated, 10 poorly differentiated; 15 adenocarcinomas, 13 well/moderately differentiated, two poorly differentiated; three rare types) were imaged at 3 T using nine b-values (0 to 800 s mm-2). Mono-exponential, stretched exponential, kurtosis, statistical, and bi-exponential models were fitted. Model preference was assessed using Bayesian Information Criterion analysis. Differences in fitted parameters between tumour types/grades and correlation between fitted parameters were assessed using two-way analysis of variance and Pearson's linear correlation coefficient, respectively. RESULTS: Non-mono-exponential models were preferred by 83 % of tumours with bi-exponential and stretched exponential models preferred by the largest numbers of tumours. Apparent diffusion coefficient (ADC) and diffusion coefficients from non-mono-exponential models were significantly lower in poorly differentiated tumours than well/moderately differentiated tumours. α (stretched exponential), K (kurtosis), f and D* (bi-exponential) were significantly different between tumour types. Strong correlation was observed between ADC and diffusion coefficients from other models. CONCLUSIONS: Non-mono-exponential models were preferred to the mono-exponential model in DW-MRI data from cervical tumours. Parameters of non-mono-exponential models showed significant differences between types and grades of tumours. KEY POINTS: • Non-mono-exponential DW-MRI models are preferred in the majority of cervical tumours. • Poorly differentiated cervical tumours exhibit lower diffusion coefficients than well/moderately differentiated tumours. • Non-mono-exponential model parameters α, K, f, and D* differ between tumour types. • Micro-structural features are likely to affect parameters in non-mono-exponential models differently.

Multiparametric functional magnetic resonance imaging for evaluation of hepatic warm ischemia-reperfusion injury in a rabbit model.

BACKGROUND: To assess the feasibility of noninvasive and quantitative evaluation of hepatic pathophysiological changes in rabbit hepatic warm ischemia-reperfusion injury (WIRI) models by using intravoxel incoherent motion (IVIM), diffusion tensor imaging (DTI) and blood oxygen level dependent (BOLD) MRI. METHODS: Twenty rabbits were randomly divided into hepatic WIRI model group and sham-operation group (n = 10 for each group). Hepatic WIRI was induced in rabbit by occluding hepatic inflow for 30 min and reperfusion for 6 h. The control group only underwent laparotomy and liver ligament dissection. IVIM with 11 b values (0 to 800 s/mm2), DTI with 2 b values (0 and 500 s/mm2) on 12 diffusion directions, and BOLD MRI with 9 TE (2.57 to 24.25 ms) were performed at 3 T clinical MR scanner. Rabbits were sacrificed for biochemical and histopathological analysis after MR scanning. All of functional MR, biochemical and histopathological parameters were analyzed by independent sample t test, Mann-Whitney U test, Pearson and Spearman correlation methods. RESULTS: All of MR parameters showed moderate to excellent interobserver reproducibility. True diffusion (Dslow), pseudodiffusion (Dfast), perfusion fraction (PF), and mean diffusitivity (MD) were lower in WIRI models than in control rabbits (P < 0.01), R2* was higher in WIRI models than in control rabbits (P < 0.001), while fractional anisotropy (FA) showed no statistical difference. There were significant differences in I score and all of biochemical parameters between the two groups (P < 0.01). Functional MR parameters corresponded well with all of biochemical parameters and some of histopathological parameters (P < 0.05). Histopathological analysis showed the structure and morphology of hepatic lobule was normal and clear in control rabbits, while diffuse hepatocyte swelling, central vein and sinusoids congestion, and inflammatory cell infiltration in WIRI models. CONCLUSIONS: IVIM, DTI, and BOLD MRI are noninvasive and useful techniques for assessing the microenvironment changes of hepatic WIRI in rabbit models.

A comparison of fitting algorithms for diffusion-weighted MRI data analysis using an intravoxel incoherent motion model.

OBJECT: The objective of this study is to propose a modified VARiable PROjection (VARPRO) algorithm specifically tailored for fitting the intravoxel incoherent motion (IVIM) model to diffusion-weighted magnetic resonance imaging (DW-MRI) data from locally advanced rectal cancer (LARC). MATERIALS AND METHODS: The proposed algorithm is compared with classical non-linear least squares (NLLS) analysis using the Levenberg-Marquardt (LM) algorithm and with two recently proposed algorithms for 'segmented' analysis. These latter two comprise two consecutive steps: first, a subset of parameters is estimated using a portion of data; second, the remaining parameters are estimated using the whole data and the previous estimates. The comparison between the algorithms was based on the [Formula: see text] goodness-of-fit measure: performance analysis was carried out on real data obtained by DW-MRI on 40 LARC patients. RESULTS: The performance of the proposed algorithm was higher than that of LM in 64 % of cases; 'segmented' methods were poorer than our algorithm in 100 % of cases. CONCLUSION: The proposed modified VARPRO algorithm can lead to better fit of the IVIM model to LARC DW-MRI data compared to other techniques.

Intravoxel incoherent motion (IVIM) analysis of vertebral bone marrow changes after radiation exposure from diagnostic imaging and interventional procedures.

Background High cumulative radiation dose in cancer patients warrants systemic examination of possible changes in bone marrow. Purpose To assess retrospectively changes in vertebral bone marrow diffusion and perfusion using intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) in hepatocellular carcinoma (HCC) patients after exposure to radiation from diagnostic imaging and interventional procedures. Material and Methods A total of 21 IVIM-DWI sets in 20 HCC patients, consisting of baseline and follow-up liver magnetic resonance imaging (MRI) with an interval less than 100 days, were reviewed after varying levels of radiation exposure from transarterial chemoembolization (TACE), multiphase liver CT, and abdominal radiography. IVIM parameters (apparent diffusion coefficient [ADC], true diffusion coefficient [D], pseudodiffusion coefficient [D*], and perfusion fraction [PF]) of vertebral bone marrow were analyzed for significant differences between baseline and follow-up MRI using Wilcoxon signed-rank test, and for correlations with cumulative effective dose, as well as time interval between last radiation exposure and follow-up MRI using Spearman's correlation. Results Compared to baseline MRI, ADC, D*, and PF significantly decreased on follow-up MRI (ADC: median [interquartile range], 0.405 × 103 mm2/s [0.364-0.477] versus 0.390 [0.348-0.461]; D*: 24.011 [18.141-29.584] versus 20.815 [15.022-28.347]; PF: 10.960% [8.828-12.985] versus 9.125 [8.606-12.803]) ( P < 0.05). There was no significant difference in D ( P = 0.807). Cumulative effective dose was moderately correlated with decrease in D* (r = 0.434). In addition, longer intervals between last exposure and follow-up MRI showed negative correlations with changes in D and ADC (r = -0.352 and -0.333, respectively). Conclusion Vertebral bone marrow diffusion and perfusion parameters were significantly changed after exposure to medical radiation.

Early evaluation of irradiated parotid glands with intravoxel incoherent motion MR imaging: correlation with dynamic contrast-enhanced MR imaging.

BACKGROUND: Radiation-induced parotid damage is one of the most common complications in patients with nasopharyngeal carcinoma (NPC) undergoing radiotherapy (RT). Intravoxel incoherent motion (IVIM) magnetic resonance (MR) imaging has been reported for evaluating irradiated parotid damage. However, the changes of IVIM perfusion-related parameters in irradiated parotid glands have not been confirmed by conventional perfusion measurements obtained from dynamic contrast-enhanced (DCE) MR imaging. The purposes of this study were to monitor radiation-induced parotid damage using IVIM and DCE MR imaging and to investigate the correlations between changes of these MR parameters. METHODS: Eighteen NPC patients underwent bilateral parotid T1-weighted, IVIM and DCE MR imaging pre-RT (2 weeks before RT) and post-RT (4 weeks after RT). Parotid volume; IVIM MR parameters, including apparent diffusion coefficient (ADC), pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f); and DCE MR parameters, including maximum relative enhancement (MRE), time to peak (TTP), Wash in Rate, and the degree of xerostomia were recorded. Correlations of parotid MR parameters with mean radiation dose, atrophy rate and xerostomia degree, as well as the relationships between IVIM and DCE MR parameters, were investigated. RESULTS: From pre-RT to post-RT, all of the IVIM and DCE MR parameters increased significantly (p < 0.001 for ADC, D, f, MRE, Wash in Rate; p = 0.024 for D*; p = 0.037 for TTP). Change rates of ADC, f and MRE were negatively correlated with atrophy rate significantly (all p < 0.05). Significant correlations were observed between the change rates of D* and MRE (r = 0.371, p = 0.026) and between the change rates of D* and TTP (r = 0.396, p = 0.017). The intra- and interobserver reproducibility of IVIM and DCE MR parameters was good to excellent (intraclass correlation coefficient, 0.633-0.983). CONCLUSIONS: Early radiation-induced changes of parotid glands could be evaluated by IVIM and DCE MR imaging. Certain IVIM and DCE MR parameters were correlated significantly.

Diagnostic utility of intravoxel incoherent motion mr imaging in differentiating primary central nervous system lymphoma from glioblastoma multiforme.

PURPOSE: To evaluate the diagnostic performance of intravoxel incoherent motion (IVIM) MR imaging and 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) in differentiating primary central nervous system lymphoma (PCNSL) from glioblastoma multiforme (GBM). MATERIALS AND METHODS: Fifty patients, 17 with PCNSL and 33 with GBM, were retrospectively studied. From the 3 Tesla IVIM data, the perfusion fraction (f) and diffusion coefficient (D) were obtained. In addition, the maximum standard uptake value (SUVmax ) was obtained from the FDG-PET data. Each of the three parameters was compared between PCNSL and GBM using Mann-Whitney U-test. The performance in discriminating between PCNSL and GBM was evaluated using receiver-operating characteristics analysis and area-under-the-curve (AUC) values for the three parameters. RESULTS: The fmax and Dmin values were significantly higher in GBM than in PCNSL (P < 0.01 and P < 0.0001, respectively). In addition, the SUVmax value was significantly lower in GBM than in PCNSL (P < 0.0005). The AUC values for fmax , Dmin , and SUVmax were 0.756, 0.905, and 0.857, respectively. The combination of the fmax and Dmin increased the diagnostic performance (AUC = 0.936) of fmax (P < 0.05), but this value was not significantly different from the values for Dmin (P = 0.30). CONCLUSION: IVIM-MR imaging noninvasively provides useful quantitative information in distinguishing between PCNSL and GBM. J. Magn. Reson. Imaging 2016;44:1256-1261.

Intravoxel incoherent motion diffusion-weighted imaging analysis of diffusion and microperfusion in grading gliomas and comparison with arterial spin labeling for evaluation of tumor perfusion.

PURPOSE: To determine the utility of intravoxel incoherent motion (IVIM) imaging in grading gliomas and compare IVIM perfusion metrics with arterial spin labeling (ASL)-derived cerebral blood flow (CBF). MATERIALS AND METHODS: Fifty-two patients with pathologically confirmed gliomas underwent IVIM and ASL imaging at 3.0T. IVIM perfusion-related diffusivity (D*), perfusion fraction (f), product of f and D*(f×D*), true diffusivity (D), and apparent diffusion coefficient (ADC) were obtained to distinguish glioma grades. The CBF derived from pseudocontinuous ASL within the solid tumor was compared and correlated with IVIM perfusion metrics for grading of gliomas. Values were also normalized to the contralateral normal-appearing white matter. Receiver-operating characteristic was performed to determine diagnostic efficiency. The reliability was estimated with intraclass coefficient, coefficient of variance, and Bland-Altman plots. RESULTS: IVIM perfusion metrics and CBF were significantly higher in the high-grade than the low-grade gliomas (P < 0.001), ADC and D were significantly lower in the high-grade than the low-grade gliomas (P < 0.001). f×D* differed significantly between grades II through IV (P < 0.05 for all). The other metrics showed significant difference between grade II and grade III (P < 0.05 for all). Area under the curve (AUC) was largest for f×D* in distinguishing high-grade from low-grade gliomas (AUC = 0.979, P < 0.001) and between grade II and grade III (AUC = 0.957, P < 0.001). f×D* improved diagnostic performance of CBF in grading gliomas and showed strong correlation with CBF (r = 0.696, P < 0.001). CONCLUSION: IVIM-derived metrics are promising biomarkers in preoperative grading gliomas. IVIM imaging may be an additive method to ASL and ADC for evaluating tumor perfusion and diffusion. J. Magn. Reson. Imaging 2016;44:620-632.

Triexponential function analysis of diffusion-weighted MRI for diagnosing prostate cancer.

BACKGROUND: To evaluate more detailed information noninvasively through on diffusion and perfusion in prostate cancer (PCa) using triexponential analysis of diffusion-weighted imaging (DWI). METHODS: Sixty-three prostate cancer patients underwent preoperative 3.0 Tesla MRI including eight b-values DWI. Triexponential analysis was performed to obtain three diffusion coefficients (Dp , Df , Ds ), as well as fractions (Fp , Ff , Fs ). Each diffusion parameter for cancerous lesions and normal tissues was compared and the relationship between diffusion parameters and Gleason score (GS) was assessed. K(trans) , Ve , and the ratios of intracellular components measured in histopathological specimens were compared with diffusion parameters. RESULTS: Dp was significantly greater for cancerous lesions than normal peripheral zone (PZ) (P < 0.001), whereas Dp in transition zone (TZ) showed no significant difference (P = 0.74, 95% confidence interval (CI) = -4.69-6.48). Ds was significantly smaller for each cancerous lesions in PZ and TZ (P < 0.001, respectively). There was no significant difference in Df between cancerous lesions and normal tissues in PZ and TZ (P = 0.07, 95% CI = -0.29-0.12 and P = 0.53, 95% CI = -3.51-2.29, respectively). D obtained with biexponential analysis were significantly smaller in cancerous lesions than in normal tissue in PZ and TZ (P < 0.001 for both), while D* in PZ and TZ showed no significant difference (P = 0.14, 95% CI = -1.60-0.24 and P = 0.31, 95% CI = -3.43-1.16, respectively). Dp in PZ and TZ showed significant correlation with K(trans) (R = 0.85, P < 0.001; R = 0.81, P < 0.001, respectively), while D(*) in PZ obtained with biexponential analysis showed no such correlation (P = 0.08, 95% CI = -0.14-0.30). Fs was significantly correlated with intracellular space fraction evaluated in histopathological specimens in PZ and TZ cancer (R = 0.41, P < 0.05; R = 0.59, P < 0.001, respectively). Ff and Fs correlated significantly with GS in PZ and TZ cancer (PZ: R = -0.44, P < 0.05; R = 0.37, P < 0.05, TZ: R = -0.59, P < 0.05; R = 0.57, P < 0.05, respectively). CONCLUSION: Triexponential analysis is a noninvasive approach that can provide more detailed information regarding diffusion and perfusion of PCa than biexponential analysis.

Role of quantitative intravoxel incoherent motion parameters in the preoperative diagnosis of nodal metastasis in patients with rectal carcinoma.

PURPOSE: To evaluate the diagnostic value of intravoxel incoherent motion imaging (IVIM) in differentiating metastatic and nonmetastatic lymph nodes in patients with rectal carcinoma. MATERIALS AND METHODS: In all, 68 patients with histologically proven rectal carcinoma underwent an IVIM sequence (b = 0, 25, 50, 75, 100, 150, 200, 400, 600, 800, 1000, 1200, 1500, and 2000 s/mm(2) ) on a 3.0T MRI scanner. The IVIM parameters (D, D*, f, and apparent diffusion coefficient [ADC] values) in metastatic and nonmetastatic lymph nodes were measured and calculated. Receiver-operating characteristic (ROC) analyses were conducted to determine the optimal thresholds, the sensitivities, and specificities for differentiation. RESULTS: Mean D, f, and ADC values of metastatic lymph nodes were significantly greater than those of the normal lymph nodes (P < 0.01), whereas the mean D* value of metastatic lymph node was statistically lower (P = 0.03). The AUC, sensitivity, specificity, and the cutoff value, respectively, for differentiating metastatic from nonmetastatic lymph nodes for D, D*, f, and ADC were as follows: D, 0.9460, 89.25%, 91.04%, and 1.14 × 10(-3) mm(2) /s; D*, 0.6930, 64.18%, 82.80%, and 7.02 × 10(-3) mm(2) /s; f, 0.7810, 92.47%, 55.22%, and 0.27%; ADC, 0.8970, 87.10%, 88.06%, and 0.80 × 10(-3) mm(2) /s. The ROC curves demonstrated that the area under the ROC (AUC) of the D, ADC, f, and D* values successively decreased, and D had the highest AUC, with D* values being lowest. CONCLUSION: An IVIM sequence may be helpful in diagnosing metastatic lymph nodes of rectal carcinoma. Average D and ADC values are more sensitive than f and D* values in this differentiation. J. MAGN. RESON. IMAGING 2016;44:1031-1039.

Use of diffusion-weighted magnetic resonance imaging to distinguish between lung cancer and focal inflammatory lesions: a comparison of intravoxel incoherent motion derived parameters and apparent diffusion coefficient.

Background Using imaging techniques to diagnose malignant and inflammatory lesions in the lung can be challenging. Purpose To compare intravoxel incoherent motion (IVIM) and apparent diffusion coefficient (ADC) magnetic resonance imaging (MRI) analysis in their ability to discriminate lung cancer from focal inflammatory lung lesions. Material and Methods Thirty-eight patients with lung masses were included: 30 lung cancers and eight inflammatory lesions. Patients were imaged with 3.0T MRI diffusion weighted imaging (DWI) using 10 b values (range, 0-1000 s/mm2). Tissue diffusivity ( D), pseudo-diffusion coefficient ( D*), and perfusion fraction ( f) were calculated using segmented biexponential analysis. ADC (total) was calculated with monoexponential fitting of the DWI data. D, D*, f, and ADC were compared between lung cancer and inflammatory lung lesions. Receiver operating characteristic analysis was performed for all DWI parameters. Results The ADC was significantly higher for inflammatory lesions than for lung cancer ([1.21 ± 0.20] × 10-3 mm2/s vs. [0.97 ± 0.15] × 10-3 mm2/s; P = 0.004). By IVIM, f was found to be significantly higher in inflammatory lesions than lung cancer ([46.10 ± 12.92] % vs. [29.29 ± 10.89] %; P = 0.005). There was no difference in D and D* between lung cancer and inflammatory lesions ( P = 0.747 and 0.124, respectively). f showed comparable diagnostic performance with ADC in differentiating lung cancer from inflammatory lung lesions, with areas under the curve of 0.833 and 0.826, sensitivity 80.0% and 73.3%, and specificity 75.0% and 87.5%, respectively. Conclusion The IVIM parameter f value provides comparable diagnostic performance with ADC and could be used as a surrogate marker for differentiating lung cancer from inflammatory lesions.