Microvascular Volume Fraction Research Articles

Combination of intravoxel incoherent motion histogram parameters and clinical characteristics for predicting response to neoadjuvant chemoradiation in patients with locally advanced rectal cancer.

To explore the value of histogram parameters derived from intravoxel incoherent motion (IVIM) for predicting response to neoadjuvant chemoradiation (nCRT) in patients with locally advanced rectal cancer (LARC). A total of 112 patients diagnosed with LARC who underwent IVIM-DWI prior to nCRT were enrolled in this study. The true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and microvascular volume fraction (f) calculated from IVIM were recorded along with the histogram parameters. The patients were classified into the pathological complete response (pCR) group and the non-pCR group according to the tumor regression grade (TRG) system. Additionally, the patients were divided into low T stage (yp T0-2) and high T stage (ypT3-4) according to the pathologic T stage (ypT stage). Univariate logistic regression analysis was implemented to identify independent risk factors, including both clinical characteristics and IVIM histogram parameters. Subsequently, models for Clinical, Histogram, and Combined Clinical and Histogram were constructed using multivariable binary logistic regression analysis for the purpose of predicting pCR. The area under the receiver operating characteristic (ROC) curve (AUCs) was employed to evaluate the diagnostic performance of the three models. The values of D_ kurtosis, f_mean, and f_ median were significantly higher in the pCR group compared with the non-pCR group (all P < 0.05). The value of D*_ entropy was significantly lower in the pCR group compared with the non-pCR group (P < 0.05). The values of D_ kurtosis, f_mean, and f_ median were significantly higher in the low T stage group compared with the high T stage group (all P < 0.05). The value of D*_ entropy was significantly lower in the low T stage group compared with the high T stage group (P < 0.05). The ROC curves indicated that the Combined Clinical and Histogram model exhibited the best diagnostic performance in predicting the pCR patients with AUCs, sensitivity, specificity, and accuracy of 0.916, 83.33%, 85.23%, and 84.82%. The histogram parameters derived from IVIM have the potential to identify patients who have achieved pCR. Moreover, the combination of IVIM histogram parameters and clinical characteristics enhanced the diagnostic performance of IVIM histogram parameters.

Investigation of perfusion impairment in degenerative cervical myelopathy beyond the site of cord compression

The aim of this study was to determine tissue-specific blood perfusion impairment of the cervical cord above the compression site in patients with degenerative cervical myelopathy (DCM) using intravoxel incoherent motion (IVIM) imaging. A quantitative MRI protocol, including structural and IVIM imaging, was conducted in healthy controls and patients. In patients, T2-weighted scans were acquired to quantify intramedullary signal changes, the maximal canal compromise, and the maximal cord compression. T2*-weighted MRI and IVIM were applied in all participants in the cervical cord (covering C1–C3 levels) to determine white matter (WM) and grey matter (GM) cross-sectional areas (as a marker of atrophy), and tissue-specific perfusion indices, respectively. IVIM imaging resulted in microvascular volume fraction (F\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$F$$\\end{document}), blood velocity (D∗\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$D^{*}$$\\end{document}), and blood flow (F·D∗\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$F \\cdot D^{*}$$\\end{document}) indices. DCM patients additionally underwent a standard neurological clinical assessment. Regression analysis assessed associations between perfusion parameters, clinical outcome measures, and remote spinal cord atrophy. Twenty-nine DCM patients and 30 healthy controls were enrolled in the study. At the level of stenosis, 11 patients showed focal radiological evidence of cervical myelopathy. Above the stenosis level, cord atrophy was observed in the WM (− 9.3%; p = 0.005) and GM (− 6.3%; p = 0.008) in patients compared to healthy controls. Blood velocity (BV) and blood flow (BF) indices were decreased in the ventral horns of the GM (BV: − 20.1%, p = 0.0009; BF: − 28.2%, p = 0.0008), in the ventral funiculi (BV: − 18.2%, p = 0.01; BF: − 21.5%, p = 0.04) and lateral funiculi (BV: − 8.5%, p = 0.03; BF: − 16.5%, p = 0.03) of the WM, across C1–C3 levels. A decrease in microvascular volume fraction was associated with GM atrophy (R = 0.46, p = 0.02). This study demonstrates tissue-specific cervical perfusion impairment rostral to the compression site in DCM patients. IVIM indices are sensitive to remote perfusion changes in the cervical cord in DCM and may serve as neuroimaging biomarkers of hemodynamic impairment in future studies. The association between perfusion impairment and cervical cord atrophy indicates that changes in hemodynamics caused by compression may contribute to the neurodegenerative processes in DCM.

Feasibility of Multiparametric Perfusion Assessment in Diabetic Foot Ulcer Using Intravoxel Incoherent Motion and Blood Oxygenation-Level Dependent MRI.

Patients with type-2 diabetes (T2DM) are at increased risk of developing diabetic foot ulcers (DFU) and experiencing impaired wound healing related to underlying microvascular disease. To evaluate the sensitivity of intra-voxel incoherent motion (IVIM) and blood oxygen level dependent (BOLD) MRI to microvascular changes in patients with DFUs. Case-control. 20 volunteers who were age and body mass index matched, including T2DM patients with DFUs (N = 10, mean age = 57.5 years), T2DM patients with controlled glycemia and without DFUs (DC, N = 5, mean age = 57.4 years) and healthy controls (HC, N = 5, mean age = 52.8 years). 3T/multi-b-value IVIM and dynamic BOLD. Resting IVIM parameters were obtained using a multi-b-value diffusion-weighted imaging sequence and two IVIM models were fit to obtain diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f) and microvascular volume fraction (MVF) parameters. Microvascular reactivity was evaluated by inducing an ischemic state in the foot with a blood pressure cuff during dynamic BOLD imaging. Perfusion indices were assessed in two regions of the foot: the medial plantar (MP) and lateral plantar (LP) regions. Effect sizes of group mean differences were assessed using Hedge's g adjusted for small sample sizes. DFU participants exhibited elevated D*, f, and MVF values in both regions (g ≥ 1.10) and increased D (g = 1.07) in the MP region compared to DC participants. DC participants showed reduced f and MVF compared to HC participants in the MP region (g ≥ 1.06). Finally, the DFU group showed reduced tolerance for ischemia in the LP region (g = -1.51) and blunted reperfusion response in both regions (g < -2.32) compared to the DC group during the cuff-occlusion challenge. The combined use of IVIM and BOLD MRI shows promise in differentiating perfusion abnormalities in the feet of diabetic patients and suggests hyperperfusion in DFU patients. 1 TECHNICAL EFFICACY: Stage 1.

Quantitative dynamic contrast-enhanced parameters and intravoxel incoherent motion facilitate the prediction of TP53 status and risk stratification of early-stage endometrial carcinoma.

The aim of the study was to investigate the value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and intravoxel incoherent motion (IVIM) in differentiating TP53-mutant from wild type, low-risk from non-low-risk early-stage endometrial carcinoma (EC). A total of 74 EC patients underwent pelvic MRI. Parameters volume transfer constant (Ktrans), rate transfer constant (Kep), the volume of extravascular extracellular space per unit volume of tissue (Ve), true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and microvascular volume fraction (f) were compared. The combination of parameters was investigated by logistic regression and evaluated by bootstrap (1000 samples), receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). In the TP53-mutant group, Ktrans and Kep were higher and D was lower than in the TP53-wild group; Ktrans, Ve, f, and D were lower in the non-low-risk group than in the low-risk group (all P < 0.05). In the identification of TP53-mutant and TP53-wild early-stage EC, Ktrans and D were independent predictors, and the combination of them had an optimal diagnostic efficacy (AUC, 0.867; sensitivity, 92.00%; specificity, 80.95%), which was significantly better than D (Z = 2.169, P = 0.030) and Ktrans (Z = 2.572, P = 0.010). In the identification of low-risk and non-low-risk early-stage EC, Ktrans, Ve, and f were independent predictors, and the combination of them had an optimal diagnostic efficacy (AUC, 0.947; sensitivity, 83.33%; specificity, 93.18%), which was significantly better than D (Z = 3.113, P = 0.002), f (Z = 4.317, P < 0.001), Ktrans (Z = 2.713, P = 0.007), and Ve (Z = 3.175, P = 0.002). The calibration curves showed that the above two combinations of independent predictors, both have good consistency, and DCA showed that these combinations were reliable clinical prediction tools. Both DCE-MRI and IVIM facilitate the prediction of TP53 status and risk stratification in early-stage EC. Compare with each single parameter, the combination of independent predictors provided better predictive power and may serve as a superior imaging marker.

Feasibility evaluation of intravoxel incoherent motion diffusion-weighted imaging in the diagnosis of skull-base invasion in nasopharyngeal carcinoma.

Objective: This study aimed to evaluate the feasibility of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) in the diagnosis of skull-base invasion (SBI) in nasopharyngeal carcinoma (NPC). Materials and methods: A total of 50 patients pathologically diagnosed with NPC and a group of 40 controls comprised of those with either normal nasopharynx or patients with nasopharyngitis underwent conventional MRI and IVIM-DWI scans with 3 different groups of b values. Among the 50 patients, 36 patients diagnosed with SBI in NPC were included in the case group according to SBI criteria. All subjects (including those in the control group and case group) were divided into the b1, b2, and b3 groups based on their b values. The pure diffusion coefficient (D), perfusion-related incoherent microcirculation (D*), and microvascular volume fraction (f) values obtained in each measurement area of each group were tested for variance. Next,2 groups of b-value parameters with statistically significant data in the 3 groups were randomly selected for use in both the control group and the case group. A t-test was performed on the D, D*, and f values obtained by measuring each area of the skull base, and the area under the curve (AUC) of the receiver operating characteristic (ROC) was used to evaluate the diagnostic efficacy of the D, D*, and f values. Results: There was no statistical significance among the D, D*, and f values of the b1 and b3 groups (P>0.05), and the differences in parameters between the b1 and b2 groups were statistically significant(P < 0.05),and the differences in parameters between the b3 and b2 groups were also statistically significant(P < 0.05).The f value of the case group, which was obtained using the b1 and b2 parameters in each area of the skull base, was lower than that of the control group (P <0.05).The D, D*, and f values of the case group obtained by the b1 and b2 parameters in the pars petrosa of the temporal bone (including the foramen lacerum) were lower than those of the control group (P<0.05).When the parameters of the b1 group were used in the corpus of sphenoid bone (including the foramen ovale), the D, D*, and f values of the control group and the case group were compared, yielding a statistically significant difference (P<0.05).When the parameters of the b1 group were used, the diagnostic efficacy of the f value in each area of the skull base was the highest (AUC=0.908-0.991), followed by the D* value (AUC=0.624-0.692). Conclusion: When the number of b values <200 s/mm2 in IVIM-DWI accounts for more than half of the selected b values, IVIM-DWI is highly stable for the diagnosis of SBI in NPC. The D, D*, and f values of the bone and muscle areas of the skull base in patients with SBI of NPC showed a downward trend, and the f value had the best diagnostic performance, followed by the D* value, while the D value had the worst. Thus, IVIM-DWI can be used as a noninvasive method in the diagnosis of SBI in NPC.

Endostatin induces normalization of blood vessels in colorectal cancer and promotes infiltration of CD8+ T cells to improve anti-PD-L1 immunotherapy

The purpose of this study was to evaluate recombinant human endostatin (rHE)-induced normalization of the tumor vasculature in colorectal cancer (CRC) and to evaluate the therapeutic effects of combined treatment with rHE and a programmed death ligand-1 (PD-L1) inhibitor. A mouse subcutaneous tumorigenesis model was established to evaluate the antitumor effects of endostatin combined with a PD-L1 inhibitor on CRC. Intravoxel incoherent motion diffusion-weighted magnetic resonance imaging (IVIM-DW MRI) was used to evaluate changes in the intratumor microcirculation in response to combined treatment with endostatin and a PD-L1 inhibitor. The infiltration density and function of CD8+ T cells in tumors were evaluated using flow cytometry. Finally, clinical specimens were used to evaluate the expression area of tumor vascular pericytes and CD8+ T cells in tumor tissues. The antitumor effects of endostatin combined with a PD-L1 inhibitor were significantly greater than those of endostatin or a PD-L1 inhibitor alone. On the ninth day of intervention, the endostatin group showed significantly higher pseudo diffusion parameter (D*) and microvascular volume fraction (F) values in tumors than those in the control group or PD-L1 group. After 27 days of intervention, the endostatin groups showed significantly lower levels of vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-β than those in the control group. Treatment of CD8+ T cells with endostatin for 24h did not alter the expression levels of markers of reduced T-cell activity. However, endostatin reversed the VEGF-mediated inhibition of the secretion of interferon (IFN)-γ from T cells. The results in CRC clinical samples showed that treatment with endostatin induced significantly higher infiltration of CD8+ T cells compared with treatment that did not include endostatin. Furthermore, the expression area of pericytes was significantly positively related to the infiltration density of CD8+ T cells and overall survival time. Endostatin improved the antitumor effects of PD-L1 inhibitors on CRC, significantly increased the activity of CD8+ T cells, and synergistically improved the tumor treatment effect of the two inhibitors.

A Nomogram of Combining IVIM-DWI and MRI Radiomics From the Primary Lesion of Rectal Adenocarcinoma to Assess Nonenlarged Lymph Node Metastasis Preoperatively.

Lymph node (LN) staging plays an important role in treatment decision-making. Current problem is that preoperative detection of LN involvement is always highly challenging for radiologists. To explore the value of the nomogram model combining intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and radiomics features from the primary lesion of rectal adenocarcinoma in assessing the non-enlarged lymph node metastasis (N-LNM) preoperatively. Retrospective. A total of 126 patients (43% female) comprising a training group (n=87) and a validation group (n=39) with pathologically confirmed rectal adenocarcinoma. A 3.0 Tesla (T); T2 -weighted imaging (T2 WI) with fast spin-echo (FSE) sequence; IVIM-DWI spin-echo echo-planar imaging sequence. Based on pathological analysis of the surgical specimen, patients were classified into negative LN (LN-) and positive LN (LN+) groups. Apparent diffusion coefficient (ADC), diffusion coefficient (D), pseudo diffusion coefficient (D*) and microvascular volume fraction (f) values of primary lesion of rectal adenocarcinoma were measured. Three-dimensional (3D) radiomics features were measured on T2 WI and IVIM-DWI. A nomogram model including IVIM-DWI and radiomics features was developed. General_univariate_analysis and multivariate logistic regression were used for radiomics features selection. The performance of the nomogram was assessed by the receiver operating characteristic (ROC) curve, calibration, and decision curve analysis (DCA). The LN+ group had a significantly lower D* value ([13.20 ± 13.66 vs. 23.25 ± 18.71] × 10-3 mm2 /sec) and a higher f value (0.43 ± 0.12 vs. 0.34 ± 0.10) than the LN- group in the training cohort. The nomogram model combined D*, f, and radiomics features had a better evaluated performance (AUC=0.864) than any other model in the training cohort. The nomogram model including IVIM-DWI and MRI radiomics features in the primary lesion of rectal adenocarcinoma was associated with the N-LNM. 4 TECHNICAL EFFICACY: Stage 2.

Parsimonious modeling of skeletal muscle perfusion: Connecting the stretched exponential and fractional Fickian diffusion.

To develop an anomalous (non-Gaussian) diffusion model for characterizing skeletal muscle perfusion using multi-b-value DWI. Fick's first law was extended for describing tissue perfusion as anomalous superdiffusion, which is non-Gaussian diffusion exhibiting greater particle spread than that of the Gaussian case. This was accomplished using a space-fractional derivative that gives rise to a power-law relationship between mean squared displacement and time, and produces a stretched exponential signal decay as a function of b-value. Numerical simulations were used to estimate parameter errors under in vivo conditions, and examine the effect of limited SNR and residual fat signal. Stretched exponential DWI parameters, α and , were measured in thigh muscles of 4 healthy volunteers at rest and following in-magnet exercise. These parameters were related to a stable distribution of jump-length probabilities and used to estimate microvascular volume fractions. Numerical simulations showed low dispersion in parameter estimates within 1.5% and 1%, and bias errors within 3% and 10%, for α and , respectively. Superdiffusion was observed in resting muscle, and to a greater degree following exercise. Resting microvascular volume fraction was between 0.0067 and 0.0139 and increased between 2.2-fold and 4.7-fold following exercise. This model captures superdiffusive molecular motions consistent with perfusion, using a parsimonious representation of the DWI signal, providing approximations of microvascular volume fraction comparable with histological estimates. This signal model demonstrates low parameter-estimation errors, and therefore holds potential for a wide range of applications in skeletal muscle and elsewhere in the body.

Quantitative study of preoperative staging of gastric cancer using intravoxel incoherent motion diffusion-weighted imaging as a potential clinical index

PurposeTo determine the utility of intravoxel incoherent motion (IVIM) diffusion-weighted imaging in quantitative analysis of preoperative tumor (T) and node (N) stages of gastric cancer, and to quantify the diagnostic threshold of IVIM parameters for serosal invasion and lymphatic metastasis. Materials and methodsFrom October 2016 to February 2020, 98 patients with gastric cancer who were receiving treatment in Zhongshan Hospital, China, were subject to an IVIM sequence imaging analysis. The IVIM sequence data were imported into software for post-processing of tumor regions of interest, and the IVIM parameters (the microvascular volume fraction (f), the molecular diffusion coefficient (D) and perfusion-related incoherent microcirculation (D*) were calculated. The variation of these IVIM parameters with different tumor-node metastasis (TNM) stages were analyzed by one-way analysis of variance. The IVIM parameters of serosal invasion and lymphatic metastasis were examined by receiver operating characteristic curve analysis and t-tests. ResultsA total of 98 gastric cancer patients (65 males and 33 females) with an average age of 61.9 years were enrolled in this study. There were 14 patients in stage T1, 14 in stage T2, 10 in stage T3 and 60 in stage T4a+b. There were 37 patients in stage N0, 19 in stage N1, 18 in stage N2 and 24 in stage N3. Statistically significant associations were found between the D values and T stages of gastric cancer. The D values of stage T4 cancers were significantly different from those of stage T2, T3 and T4 cancers. The D value decreased with increasing T stage. The mean D values of stages were 1.432 × 10−3 mm2/s (T1), 1.225 × 10−3 mm2/s (T2), 1.154 × 10−3 mm2/s (T3) and 0.9468 × 10−3 mm2/s (T4). The extent of the invasion of serosa was found to be significantly correlated with D value, with the diagnostic threshold for D being 1.107 × 10−3 mm2/s. In addition, different pathological N stages of gastric cancer lesions showed statistically significantly variations in f values, but no correlation was found with different N stages. Finally, the extent of lymphatic metastasis was found to be correlated with D values, with the diagnostic threshold being 1.1739 × 10−3 mm2/s. There was no statistically significant correlation between the IVIM MRI parameters and tumor size. The grade of tumor was found to be significantly correlated with D* value, with the diagnostic threshold for D* being 1.516 × 10−2 mm2/s. There was no statistically significant correlation between the ADC value and tumor size. There was a significant difference in the ADC values among different T and N stage cancers. ADC value had statistically significant to distinguish gastric cancer with or without serosal invasion, its detection efficiency was not as high as that of D value, with an AUC of 0.628 and 0.830, respectively. The ADC value was not statistically significant in distinguishing gastric cancer with or without lymphatic metastasis (P ≥ 0.05). The ADC value had not statistically significant in distinguishing gastric cancer between low and medium-high grade (P ≥ 0.05). ConclusionWe found that significant differences existed between whole-volume IVIM parameters of different T or N stages in gastric cancers, and were able to quantify different T or N stages of gastric cancer by the values of these parameters. The results of this quantitative study provide new tools for evaluating the prognosis of gastric cancer and will be valuable for the development of an new imaging method for determining the morphological stages of gastric cancer.

Predictive Ki-67 Proliferation Index of Cervical Squamous Cell Carcinoma Based on IVIM-DWI Combined with Texture Features.

Purpose This study aims to determine whether IVIM-DWI combined with texture features based on preoperative IVIM-DWI could be used to predict the Ki-67 PI, which is a widely used cell proliferation biomarker in CSCC. Methods A total of 70 patients were included. Among these patients, 16 patients were divided into the Ki-67 PI <50% group and 54 patients were divided into the Ki-67 PI ≥50% group based on the retrospective surgical evaluation. All patients were examined using a 3.0T MRI unit with one standard protocol, including an IVIM-DWI sequence with 10 b values (0–1,500 sec/mm2). The maximum level of CSCC with a b value of 800 sec/mm2 was selected. The parameters (diffusion coefficient (D), microvascular volume fraction (f), and pseudodiffusion coefficient (D∗)) were calculated with the ADW 4.6 workstation, and the texture features based on IVIM-DWI were measured using GE AK quantitative texture analysis software. The texture features included the first order, GLCM, GLSZM, GLRLM, and wavelet transform features. The differences in IVIM-DWI parameters and texture features between the two groups were compared, and the ROC curve was performed for parameters with group differences, and in combination. Results The D value in the Ki-67 PI ≥50% group was lower than that in the Ki-67 PI <50% group (P < 0.05). A total of 1,050 texture features were obtained using AK software. Through univariate logistic regression, mPMR feature selection, and multivariate logistic regression, three texture features were obtained: wavelet_HHL_GLRLM_ LRHGLE, lbp_3D_k_ firstorder_IR, and wavelet_HLH_GLCM_IMC1. The AUC of the prediction model based on the three texture features was 0.816, and the combined D value and three texture features was 0.834. Conclusions Texture analysis on IVIM-DWI and its parameters was helpful for predicting Ki-67 PI and may provide a noninvasive method to investigate important imaging biomarkers for CSCC.

Intravoxel Incoherent Motion Imaging in Differentiation Borderline From Malignant Ovarian Epithelial Tumors: Correlation With Histological Cell Proliferation and Vessel Characteristics.

The differentiation of borderline from malignant ovarian epithelial tumors (OETs) is difficult based on morphologic characteristics. Diffusion and perfusion information from intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) might be useful for this distinction. To investigate the potential of IVIM-DWI in discriminating borderline from malignant OETs by correlating with cell proliferation and microvessel density (MVD). Prospective. Sixty-six patients with OETs (22 borderline, BOETs; 44 malignant, MOETs) underwent IVIM-DWI before surgery. 3.0T IVIM-DWI sequence with 12 b-values (0-1000 sec/mm2 ). Apparent diffusion coefficient (ADC) and IVIM-DWI parameters (diffusion coefficient [D], microvascular volume fraction [f], and pseudodiffusion coefficient [D*]) were measured. Cell proliferation and MVD was determined by immunohistochemical staining of Ki-67 and CD-31, respectively. Mann-Whitney U-test; two-sample t-test; intraclass correlation coefficient; Bland-Altman analysis; receiver operating characteristics (ROC) curves; and Spearman correlation. ADC and D in BOETs was significantly higher than those in MOETs (P < 0.001), while f in BOETs was significantly lower than those in MOETs (P < 0.001). No significant difference was found in D* between borderline and malignancies (P = 0.324). In the differential diagnosis of borderline from malignant OETs; D demonstrated the highest area under the curve (AUC) of 0.951, while ADC and f had a lower AUC of 0.921 and 0.847, respectively. The ADC and D was negatively correlated with cell proliferation (r = -0.682, r = -0.694, respectively, P < 0.001), while f was positively correlated with MVD of the OETs (r = 0.558, P < 0.001). IVIM-DWI may be a useful tool for differentiating BOETs from MOETs. D and f could be image biomarkers to reflect histopathological characteristics of cell proliferation and MVD in OETs. 1 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:928-935.

Intravoxel incoherent motion diffusion-weighted imaging of resectable oesophageal squamous cell carcinoma: association with tumour stage.

To determine whether intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) derived parameters can be associated with tumour stage of oesophageal squamous cell carcinoma (SCC). 60 patients with resectable oesophageal SCC and 20 healthy individuals underwent oesophageal DWI-using multi b-values with a 3.0 T MR system. Pure diffusion coefficient (D), perfusion-related incoherent microcirculation (D*), microvascular volume fraction (f) and apparent diffusion coefficient (ADC) were measured on DWI. Statistical analyses were performed to determine associations of DWI-derived parameters with T-stage. ADC (r = -0.842), D (r = -0.729), D* (r = -0.301) and f (r = -0.817) were negatively correlated with T-stage of oesophageal SCC (all p < 0.01), and the multinominal regression analyses revealed that IVIM-derived parameters including D (p = 0.038; odds ratio <1) and f (p < 0.001; odds ratio <1) were associated with T-stage. The Mann-Whitney U tests with Bonferroni correction showed that D, f and ADC could discriminate oesophageal SCC, especially T1-staged tumour, from normal oesophagus (all p < 0.05) while D* could not (p > 0.05). By receiver operating characteristic analyses, f could be the best indicator for detecting oesophageal SCC with an area under receiver operating characteristic (AUC) of 0.964, especially T1-staged cancer with an AUC of 0.984, and for discriminating T1-stages between T0-1 and T2-3 with an AUC of 0.957, and between T0-2 and T3 with an AUC of 0.945 in comparison with any other DWI-derived parameter. IVIM derived parameters can be associated with T-stage of oesophageal SCC. Advances in knowledge (1) IVIM-derived parameters are negatively correlated with stage of oesophageal SCC. (2) Among IVIM-derived parameters, microvascular volume fraction helps detect and stage oesophageal SCC.

Simple and reliable determination of intravoxel incoherent motion parameters for the differential diagnosis of head and neck tumors.

Intravoxel incoherent motion (IVIM) imaging can characterize diffusion and perfusion of normal and diseased tissues, and IVIM parameters are authentically determined by using cumbersome least-squares method. We evaluated a simple technique for the determination of IVIM parameters using geometric analysis of the multiexponential signal decay curve as an alternative to the least-squares method for the diagnosis of head and neck tumors. Pure diffusion coefficients (D), microvascular volume fraction (f), perfusion-related incoherent microcirculation (D*), and perfusion parameter that is heavily weighted towards extravascular space (P) were determined geometrically (Geo D, Geo f, and Geo P) or by least-squares method (Fit D, Fit f, and Fit D*) in normal structures and 105 head and neck tumors. The IVIM parameters were compared for their levels and diagnostic abilities between the 2 techniques. The IVIM parameters were not able to determine in 14 tumors with the least-squares method alone and in 4 tumors with the geometric and least-squares methods. The geometric IVIM values were significantly different (p<0.001) from Fit values (+2±4% and −7±24% for D and f values, respectively). Geo D and Fit D differentiated between lymphomas and SCCs with similar efficacy (78% and 80% accuracy, respectively). Stepwise approaches using combinations of Geo D and Geo P, Geo D and Geo f, or Fit D and Fit D* differentiated between pleomorphic adenomas, Warthin tumors, and malignant salivary gland tumors with the same efficacy (91% accuracy = 21/23). However, a stepwise differentiation using Fit D and Fit f was less effective (83% accuracy = 19/23). Considering cumbersome procedures with the least squares method compared with the geometric method, we concluded that the geometric determination of IVIM parameters can be an alternative to least-squares method in the diagnosis of head and neck tumors.

Intravoxel Incoherent Motion Imaging of Masticatory Muscles: Pilot Study for the Assessment of Perfusion and Diffusion During Clenching

The purpose of this study was to evaluate intravoxel incoherent motion (IVIM) imaging for assessing perfusion and diffusion of masticatory muscles during clenching. A prospective study was performed to assess the perfusion and diffusion of masticatory muscles during clenching. The masseter and medial pterygoid muscles participate in clenching, and the lateral pterygoids do not. IVIM parameters (microvascular volume fraction, f; pure diffusion coefficient, D; and perfusion-related incoherent microcirculation, D*) were determined on both the clenching and the balancing sides in 24 volunteers. The Wilcoxon test was used to compare the IVIM parameters at rest and during clenching. The f and D* values of the masseters significantly increased on the clenching side (f = 0.17 ± 0.10 vs 0.29 ± 0.11, p < 0.001; D* = 21.3 ± 18.5 × 10(-3) mm(2)/s vs 42.1 ± 33.3 × 10(-3) mm(2)/s, p = 0.0008). However, the D values did not change during clenching (1.26 ± 0.23 × 10(-3) mm(2) vs 1.21 ± 0.35 × 10(-3) mm(2)). The f values of the medial pterygoids also increased on the clenching side (0.20 ± 0.09 vs 0.30 ± 0.09, p < 0.001). On the balancing side, the f values of the masseters (0.19 ± 0.12 vs 0.30 ± 0.12, p < 0.001) and medial pterygoids (0.20 ± 0.09 vs 0.29 ± 0.11, p = 0.0007) significantly increased during clenching. In contrast, the IVIM values of the lateral pterygoids did not change. IVIM imaging may be useful for assessing perfusion and diffusion of the masticatory muscles.

Salivary Gland Tumors: Use of Intravoxel Incoherent Motion MR Imaging for Assessment of Diffusion and Perfusion for the Differentiation of Benign from Malignant Tumors

To prospectively evaluate the intravoxel incoherent motion (IVIM) parameters (microvascular volume fraction, f; pure diffusion coefficient, D; and perfusion-related incoherent microcirculation, D*) for differentiating between benign and malignant salivary gland tumors. All participants in this prospective institutional review board-approved study provided written informed consent. The perfusion and diffusion of 20 (65%) benign (12 pleomorphic adenomas and eight Warthin tumors) and 11 (35%) malignant salivary gland tumors were assessed on the basis of the IVIM theory. Diffusion-weighted magnetic resonance imaging was performed by using 11 b values (0-800 sec/mm(2)). The IVIM parameters of the salivary gland tumors were determined by a radiologist, and significant differences between the tumor types were assessed by using the Steel-Dwass test. The f values of Warthin tumors (0.156 ± 0.039 [standard deviation]) were significantly larger than those of pleomorphic adenomas (0.066 ± 0.031) (P = .003). The D values of malignant tumors (0.96 × 10(-3) mm(2)/sec ± 0.22) were significantly different from those of benign tumors (pleomorphic adenomas, 1.38 × 10(-3) mm(2)/sec ± 0.30 [P = .002]; Warthin tumors, 0.61 × 10(-3) mm(2)/sec ± 0.11 [P = .005]). The D* values of malignant tumors (21.99 × 10(-3) mm(2)/sec ± 19.01) were significantly smaller than those of Warthin tumors (42.64 × 10(-3) mm(2)/sec ± 20.17) (P = .022). The combination of D and D* criteria provided the best diagnostic accuracy (100%) for differentiation among the three tumor types. IVIM imaging may be helpful for differentiation between benign and malignant salivary gland tumors.

Intravoxel partially coherent motion technique: Characterization of the anisotropy of skeletal muscle microvasculature

To propose a reformulation of the intravoxel incoherent motion (IVIM) technique exploiting the low b-value diffusion-weighted imaging regime that can characterize microcirculation of tissues perfused with partially coherent blood flow. The new methodology, termed intravoxel partially coherent motion (IVPCM) technique, is suitable for probing microcirculation in tissues with ordered microvasculature, such as skeletal muscle. We employ a subvoxel model utilizing a randomly oriented bundle of straight vessels whose orientation statistics are characterized by a Fisher axial distribution with concentration parameter K quantifying the anisotropy of the distribution (K = 0 indicates isotropic capillary orientation). The methodology is first validated with a proof-of-principle phantom experiment and is then applied to analyze the microvasculature of human calf muscle at rest. The microcirculatory part of the diffusion-weighted signal at b < 200 s/mm(2) is anisotropic. The variation of the diffusion-weighted signal with b-value exhibits stronger deviation from the expected monoexponential decay when the diffusion encoding gradient is applied parallel to the mean myofiber direction in the calf muscle of three healthy volunteers. The application of the model to data from the medial gastrocnemius and the soleus of the three volunteers gives results within the expected range for the mean microvascular volume fraction, the mean microflow velocity, and the parameter K. The proposed methodology has the capability of characterizing the anisotropy of the capillary network in vivo in a manner analogous to the capability of high b-value diffusion to characterize the anisotropy of muscle fibers.

Novel Rat Model of Ischemic Cardiomyopathy Induced by Repetitive Myocardial Ischemia/Reperfusion Injury While Conscious

A rodent model of ischemic cardiomyopathy (ICM) induced by repetitive brief ischemia/reperfusion (I/R) injury while conscious has not been previously established. A newly developed coronary occluder was implanted in male Wistar rats. A repetitive I/R protocol (20 s, 2 min, followed by main 30 min--ischemia, every 48 h, for 4 weeks) was introduced while the animals were conscious. The I/R protocol did not induce transmural scar formation but induced (1) residual myocytes with scattered infiltration of fibrosis (Masson trichrome stain), (2) coronary hypoperfusion ((201)Tl-Cl autoradiogram), (3) reduced coronary microvascular volume fraction (microCT), and (4) gradually progressive left ventricular (LV) dilation (echocardiography). These parameters of ICM showed interindividual variation; however, the percent increase in LV diastolic area on day 3 was significantly correlated with LV dilation (r=0.91, p<0.0001), fibrosis (r=0.77, p=0.0034), and reduction in microvessels (r=0.67, p=0.040) at week 4. The LV dilatory response on day 3 also correlated with inducible nitric oxide synthase expression (immunohistochemistry, day 3) in the LV (r=0.92, p=0.028). A novel rat model of ICM induced by repetitive I/R while conscious showed interindividual variation in the severity of ICM in the advanced stage, but this was predictable non-invasively (by LV dilatory response) during the initial stage of repetitive I/R.

Morphometry of the Subepithelial Circulation in Sheep Airways: Effect of Vascular Congestion

In order to quantitate the subepithelial microvascular volume and its relation to the airway lumen, we conducted a morphometric analysis of the vascular compartment in the wall of the trachea (within a 55-microns depth from the epithelial basement membrane) and of 1.0 and 0.5-mm bronchioles of sheep. The lungs were fixed by bronchial and pulmonary artery perfusion with glutaraldehyde under three experimental conditions: (1) bronchial artery pressure, 100 mm Hg pulmonary artery pressure, 20 mm Hg (control); (2) bronchial artery pressure, 100 mm Hg, pulmonary artery pressure, 40 mm Hg (pulmonary hypertension, PH); (3) bronchial artery pressure, 100 mm Hg, pulmonary artery pressure, 40 mm Hg (pharmacologic vasodilation with sodium nitroprusside, PH + V). Venous pressures were atmospheric. Under control conditions, the microvascular volume fraction comprised 12, 16, and 15% of the subepithelial tissue in the trachea and 1-mm and 0.5-mm bronchioles, respectively. PH increased the microvascular volume fraction in the bronchioles (p less than 0.05), but it had no effect on the microvasculature in the trachea. PH + V approximately doubled the microvascular volume fraction in the trachea and the bronchioles. PH increased the mean wall thickness, and PH and PH + V decreased the airway cross-sectional area in the 1-mm bronchioles. These observations demonstrate that the microvasculature constitutes a considerable volume fraction of the subepithelial airway tissue and that vascular congestion can narrow the bronchiolar lumen.