True Diffusion Coefficient Research Articles

Prediction of Neoadjuvant Radiotherapy and Chemotherapy for Locally Advanced Rectal Cancer Based on 3.0T MRI Intravoxel Incoherent Motion Diffusion Weighted-Imaging with Fe3O4 Nanocontrast Agent

The purpose of this study was to preliminarily explore the feasibility of pre-treatment intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) for predicting the efficacy of neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC). Fifty-four patients underwent preoperative IVIM-DWI before (pre-nCRT) and after nCRT (post-nCRT). The values of pre-nCRT and post-nCRT IVIM-DWI parameters (apparent diffusion coefficient standard (ADC), true diffusion coefficient (D), pseudodiffusion coefficient (D*) and perfusion fraction (f), together with the percentage changes (Δ% parametric value) induced by nCRT, were compared between pathological complete response (pCR) and non-pCR groups. After nCRT, the ADC and Dvalues for LARC increased significantly (all P <0.05). The TRG score revealed positive correlations with pre f (r = 0.357, P = 0.020), postD (r =0.551,P <0.001), and Δ%D (r =0.605, P <0.001). The pCR group (n =10) had higher preD *, pref, postD, Δ%ADC, and Δ%D values than the non-pCR group (n =32) (allP <0.05). The GR group (n =15) exhibited higher postD, %ADC, and %D values than the PR group (n =27) (allP <0.05). Based on ROC analysis, Δ%D had a higher area under the curve value than Δ%ADC (P =0.009) in discriminating the pCR and non-pCR groups. IVIM-DWI may be helpful in identifying pCR to nCRT for LARC and is more accurate than traditional DWI.

Evaluation of Diffusion-Weighted MRI and FDG-PET/CT to Assess Response to AdCD40L treatment in Metastatic Melanoma Patients

The purpose was to evaluate the potential of diffusion-weighted-magnetic resonance imaging (DW-MRI) and 18F-fludeoxy-glucose-positron emission tomography integrated with CT (FDG-PET/CT) for prediction of overall survival (OS) following AdCD40L-immunotherapy in patients with metastatic malignant melanoma (MMM). Twenty-four patients with refractory MMM were treated with immunostimulatory AdCD40L gene therapy in a phase I/IIa study. Pre-therapeutic DW-MRI and FDG-PET/CT were performed and then repeated at 5 and 9 weeks post-treatment. Evaluation was conducted according to RECIST 1.1 and EORTC criteria. Apparent diffusion coefficient (ADC), true diffusion coefficient (D), maximum standardized uptake value (SUVmax) were measured in the injected lesions. Fold changes (F) in ADC (F ADC), D (F D), SUVmax (F SUVmax) were statistically assessed. F D ≥ 1 and F ADC ≥ 1 were associated with better OS in scans at week 5 and 9 respectively. F SUVmax was not correlated to OS. F ADC ≥ 1 in both post-treatment scans and F D ≥ 1 at week 5 were related to a significant decrease of size of the injected lesions. These results suggest that in patients with MMM treated with AdCD40l, functional parameters of DW-MRI are better early predictors of OS than the established metabolic and morphologic criteria for FDG-PET/CT and MRI, respectively.

Correlation of Intravoxel Incoherent Motion Parameters and Histological Characteristics From Infiltrated Marrow in Patients With Acute Leukemia.

An accurate and noninvasive method is of great importance to assess angiogenesis and cellularity of bone marrow in acute leukemia (AL). To investigate whether the intravoxel incoherent motion (IVIM) parameters correlate with the histological characteristics of infiltrated marrow in AL patients and compare the difference between acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Prospective. Forty newly diagnosed patients with AL, including 20 AML and 20 ALL. 1.5T/T1 WI and IVIM. IVIM-derived parameters (true diffusion coefficient D, pseudodiffusion coefficient D*, and perfusion fraction, f) were measured in lumbar marrow. Histopathological analyses were performed from samples of marrow biopsy. The correlations between IVIM parameters and histological parameters used the Spearman correlation test. The difference of IVIM parameters and histological parameters between ALL and AML groups used the unpaired t-test or Mann-Whitney U-test, as appropriate. The f was positively correlated with microvessel density (MVD) in patients with ALL, AML, and AL (r = 0.740, P = 0.006; r = 0.771, P < 0.001; and r = 0.750, P < 0.001, respectively). There were no significant correlations between D and bone marrow cellularity in the three groups (r = -0.289, P = 0.362; r = 0.281, P = 0.292; and r = 0.058, P = 0.769, respectively). D and f values of ALL were higher than that of AML group (t = 3.332, P = 0.003 and t = 2.600, P = 0.014, respectively). MVD was higher in ALL than AML (t = 2.120, P = 0.044), whereas bone marrow cellularity had no significant difference between AML and ALL (t = -0.682, P = 0.501). The f value derived from IVIM in bone marrow was positively correlated with MVD, while f might be able to show a difference of vascularity between ALL and AML. Therefore, the f value can be used as an alternative imaging marker of angiogenesis in marrow of AL patients. 1 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2020;51:1720-1726.

Intravoxel incoherent motion imaging for diagnosing and staging the liver fibrosis and inflammation.

To evaluate the diagnostic accuracy of intravoxel incoherent motion (IVIM) model parameters for the diagnosis and staging of liver fibrosis and inflammation in patients with chronic hepatitis B. Fifty-four patients with chronic hepatitis B and 42 healthy volunteers were included in the study. All subjects were examined by 3 T magnetic resonance imaging. Diffusion-weighted imaging was undertaken with sixteen b values. IVIM parameters [D (true diffusion coefficient), D* (pseudo-diffusion coefficient), f (perfusion fraction)] were calculated. Histological evaluation of biopsy samples was considered the reference standard for the staging of liver fibrosis and inflammation. Differences in IVIM parameters between patient and control groups were analyzed. In the patient group, fibrosis stage and inflammation grade groups were analyzed with respect to IVIM parameters. The correlation was assessed between IVIM parameters and Ishak-modified scale of fibrosis stages and inflammation grades. The D was significantly lower in the patient group than the control group, p = 0.038 with Cohen's d effect size of 0.452. D was significantly different between fibrosis stage levels. D values decreased in fibrosis stages from the minimal to moderate to marked fibrosis. Fibrosis grades significantly negatively correlated with D and D* values, p = 0.001, and 0.021, respectively. In addition, inflammation grades negatively correlated with f values, p = 0.047. D values measured with IVIM imaging may help to diagnose liver fibrosis. IVIM imaging could be an alternative to liver biopsy for the staging of liver fibrosis.

Differential detection of metastatic and inflammatory lymph nodes using intravoxel incoherent motion diffusion-weighted imaging

PurposeThis study sought to monitor the dynamic process of lymph node (LN) metastasis with intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI), and to investigate the impact of disease course on the detection of metastatic LNs by IVIM-DWI. MethodsTwenty female New Zealand rabbits with 2.5–3.0 kg body weight were studied. VX2 cells and egg yolk emulsion were randomly inoculated into one thigh to induce metastatic and inflammatory popliteal LNs, respectively. Eight rabbits underwent IVIM-DWI (14 b values, 0–2000 s/mm2) 2 h prior to, and 14, 21, and 28 days after inoculation (D0, D14, D21, D28). The apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) were measured and compared between the metastatic and the inflammatory groups at each time point. Three rabbits randomly chosen from the remaining twelve rabbits were sacrificed at each time point to perform hematoxylin and eosin staining and histologic evaluation. ResultsThe patterns of dynamic change of D*, ADC, and D were different between the metastatic and the inflammatory LNs. The metastatic group had a lower D* value at D14 (p = .003), and greater ADC and D values at both D21 (p = .001, p = .001) and D28 (p = .021, p = .001), compared to the inflammatory group. The f value of the metastatic group was greater than that of the inflammatory only at D28 (p = .001). ConclusionsIVIM-DWI can reflect the dynamic process of LN metastasis, and disease course has a significant influence on the ability of IVIM-DWI to detect metastatic nodes.

Use of intravoxel incoherent motion imaging to monitor a rat kidney chronic allograft damage model

BackgroundChronic allograft damage (CAD) is the leading cause of long-term graft dysfunction. A noninvasive method that can diagnose CAD early and monitor its development is needed.MethodsKidneys from Fisher rats were transplanted into Lewis rats to establish a CAD model (n = 20). The control group underwent syngeneic kidney transplantation (n = 20). The serum creatinine of the rats was monitored. At 4, 12, and 20 weeks after modeling, a magnetic resonance imaging (MRI) examination was performed. The apparent diffusion coefficient (ADC), pseudo diffusion coefficient (D*), true diffusion coefficient (D) and perfusion fraction (f) of the two groups were analyzed. Chronic allograft damage index (CADI) scoring was used to evaluate the transplanted kidney specimens. Immunohistochemistry was used to detect the expression of fibrosis markers in the transplanted kidney tissues and to analyze their correlations with all MRI parameters.ResultsThe transplanted kidneys in the experimental group developed CAD changes before the appearance of elevated creatinine. The MRI parameters in the experimental group [ADC (1.460 ± 0.109 VS 2.095 ± 0.319, P < 0.001), D (1.435 ± 0.102 VS 1.969 ± 0.305, P < 0.001), and f (26.532 ± 2.136 VS 32.255 ± 4.013, P < 0.001)] decreased, and D* (20.950 ± 2.273 VS 21.415 ± 1.598, P = 0.131) was not significantly different from those in the control group. ADC, D and f were negatively correlated with the CADI and the α-SMA and vimentin expression levels.ConclusionIntravoxel incoherent motion (IVIM) imaging could detect CAD earlier than creatinine and reflect the degree of fibrosis in grafts quantitatively.

Intravoxel incoherent motion magnetic resonance imaging for assessment of chronic pancreatitis with special focus on its early stage.

Background It is clinically necessary to validate a new non-invasive and reliable imaging method to detect early chronic pancreatitis. Intravoxel incoherent motion magnetic resonance imaging (MRI) is useful for quantitative assessment in abdominal solid organs. Purpose To investigate the usefulness of intravoxel incoherent motion MRI parameters in the diagnosis of chronic pancreatitis. Material and Methods Sixty patients with early chronic pancreatitis (n = 44) and chronic pancreatitis (n = 16) were assessed with intravoxel incoherent motion imaging. For comparison, a control group of 71 individuals without chronic pancreatitis was also enrolled. The perfusion fraction (f), pseudo-diffusion coefficient (D*), true diffusion coefficient (D), and apparent diffusion coefficient of pancreatic parenchyma were calculated. These measurements were compared between the three groups. The diagnostic accuracy of imaging parameters was assessed. Results The f values of the early chronic pancreatitis group and the chronic pancreatitis group were significantly lower than those of the control group ( P &lt; 0.001 and P &lt; 0.001, respectively). The D* value of the chronic pancreatitis group was significantly lower than that of the early chronic pancreatitis group ( P = 0.0025). The D values of the early chronic pancreatitis group and the chronic pancreatitis group were significantly higher than those of the control group ( P = 0.001 and P = 0.001, respectively). The perfusion fraction showed the highest diagnostic performance with an Az value of 0.76 for discriminating the control group from the early chronic pancreatitis and chronic pancreatitis groups. Conclusion Intravoxel incoherent motion MRI parameters may reflect the minimal histological changes in early chronic pancreatitis.

Intravoxel Incoherent Motion Parameters for Assessing the Efficiency of Locoregional Bridging Treatments before Liver Transplantation

ObjectiveTo evaluate the diagnostic accuracy of Intravoxel Incoherent Motion (IVIM) parameters for assessment of tumor response after locoregional treatment (LRT) of hepatocellular carcinoma (HCC). MethodsFifteen patients with HCC who had undergone LRTs (11 transarterial radioembolization, 4 transarterial chemoembolization) were included. In addition to routine upper abdominal magnetic resonance imaging sequences, IVIM with 16 different b values and conventional diffusion weighted imaging with 3 different b factors were obtained immediately before and 8 weeks after LRTs. Magnetic resonance imaging response was evaluated according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) and HCCs were categorized into 2 subgroups, responders and nonresponders. Quantitatively, the number of diffusion-changes were calculated with apparent diffusion coefficient (ADC) and IVIM parameters, including mean D (true diffusion coefficient), pseudo-diffusion coefficient associated with blood flow, and f (perfusion fraction) values. Subsequently, the pre- and post-treatment parameters were compared using the Mann-Whitney U test. ResultsConsidering all HCCs, a significant decrease was observed according to mRECIST criteria (–38.43 ± 16.49). The ADC and D values after LRTs were significantly higher than those of the preceding ones. The f values after LRTs were significantly lower than those of pre-treatment. In the responders group, ADC and D values were significantly increased and f values were significantly decreased after LRTs. No difference of statistical significance was achieved in the nonresponders group. ConclusionsADC values and IVIM parameters appear to reflect the response of LRTs as effectively as those of mRECIST. This promises new horizons in the management of pretransplant patients, especially in renal insufficiency clinical settings, owing to the elimination of contrast media administration.

Correlation of apparent diffusion coefficient and intravoxel incoherent motion imaging parameters with Ki-67 expression in extrahepatic cholangiocarcinoma

PurposeTo investigate the correlation of magnetic resonance imaging (MRI), apparent diffusion coefficient (ADC) and intravoxel incoherent motion imaging parameters with Ki-67 expression in cholangiocarcinoma. MethodsA total of 42 extrahepatic cholangiocarcinoma (EHCC) cases confirmed by surgical pathology were analyzed retrospectively. Subjects underwent MRI at 3.0 T and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) sequential scanning prior to surgery, and postoperative Ki-67 expression was recorded by immunohistochemistry (IHC). The patients were divided into 4 groups (I–IV) based on increasing Ki-67 expression from − to +++. ADC values and IVIM-DWI parameters were calculated, including true diffusion coefficient (D), perfusion fraction (f), and pseudo-diffusion coefficient (D*). The comparison among groups was analyzed by univariate ANOVA (normal distribution) or Kruskal-Wallis H (non-normal distribution). Spearman correlation analysis was used to analyze the correlation of each parameter with Ki-67 expression. The diagnostic efficiency of each parameter was compared using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. ResultsExcept for D*, other values had statistically significant differences between groups (P < 0.05). ADC, D and f values had negative correlations with Ki-67 expression (r values were −0.607, −0.795, −0.531, respectively, P < 0.05). The AUCs were 0.701, 0.880, 0.623, respectively (P < 0.0001). ConclusionIVIM-DWI technology can reflect the proliferative activity of EHCC cells to a certain extent, and has clinical value for predicting the degree of malignancy of a tumor.

Value of Intravoxel Incoherent Motion for Hepatocellular Carcinoma Grading

BackgroundTo evaluate the diagnostic accuracy of intravoxel incoherent motion (IVIM) parameters in estimation of hepatocellular carcinoma (HCC) grading. Materials and methodsTwenty-nine patients with histopathologically diagnosed as 42 HCC at explant were included in this retrospective study. All patients were examined by 1.5T magnetic resonance imaging with the use of 4-channel phased array body coil. In addition to routine pre- and postcontrast sequences, IVIM (16 different b factors varying from 0 to 1300 s/mm2) and conventional diffusion-weighted imaging (3 different b factors of 50, 400, 800 s/mm2) were obtained with single-shot echo planar spin echo sequence. Apparent diffusion coefficient (ADC) and IVIM parameters including mean D (true diffusion coefficient), D* (pseudo-diffusion coefficient associated with blood flow), and f (perfusion fraction) values were calculated. Histopathologically, HCC was classified as low (grade 1, 2) and high (grade 3, 4) grade in accordance with the Edmondson-Steiner score. Quantitatively, ADC, D, D*, and f values were compared between the low- and high-grade groups by Student t test. The relationship between the parameters and histologic grade was analyzed using the Spearman’s correlation test. To evaluate the diagnostic performance of the parameters, receiver operating characteristic analysis was performed. ResultsHigh-grade HCCs had significantly lower ADC and D values than low grade groups (P = .005 and P = .026, retrospectively); ADC and D values were inversely correlated with tumor grade (r = –0.519, P = .011, r = –0.510, P = .026, respectively). High-grade HCCs had significantly higher f values when compared with the low-grade group (P = .005). The f values were positively correlated with tumor grade (r = 0.548, P = .007). The best discriminative parameter was f value. Cut-off value of 32% of f values showed sensitivity of 75.6% and a specificity of 73.5%. ConclusionADC values and IVIM parameters such as f values appear to reflect the grade of HCCs.

Evaluation of intravoxel incoherent motion-diffusion weighted imaging in predicting early recurrence of hepatocellular carcinoma after curative hepatectomy

Objective To investigate the value of preoperative intravoxel incoherent motion-diffusion weighted imaging (IVIM-DWI) in predicting early recurrence of hepatocellular carcinoma (HCC) after curative hepatectomy. Methods The clinical data of 51 HCC patients who underwent curative hepatectomy at Beijing Tsinghua Changgung Hospital, Tsinghua University from December 2014 to March 2017 were retrospectively analyzed. The study included 45 males and 6 females, aged 56.4±10.1. The patients were divided into the early-recurrence group (21 patients) and the non-recurrence group (30 patients) according to whether there was HCC recurrence within 1 year after curative hepatectomy. The parameters of the lesions were measured and calculated: the apparent diffusion coefficient (ADC) value, true diffusion coefficient (D) value, perfusion-related diffusion coefficient (D*) value and perfusion fraction (f) value. Receiver operating characteristic curves (ROC) were used to evaluate the prediction efficiency of the parameters. Results The ADC and D values of the early-recurrence group were significantly lower than the non-recurrence group. The differences were statistically significant (P<0.05). In predicting early recurrence of HCC after curative hepatectomy, the ADC values showed the area under ROC was 0.713 (95% CI: 0.572~0.855), the sensitivity was 0.857 and specificity was 0.567 when the optimal threshold value was 1.24×10-3mm2/s. The D values in predicting early recurrence demonstrated the area under ROC was 0.740 (95% CI: 0.602~0.877), the sensitivity was 0.905 and specificity was 0.600 when the optimal threshold value was 1.03×10-3mm2/s. Conclusions The ADC and D values of IVIM-DWI could provide evidence in predicting early recurrence of HCC after curative hepatectomy. The D values had a higher prediction efficiency. Key words: Carcinoma, hepatocellular; Hepatectomy; Recurrence; Diffusion weighted imaging

Intravoxel incoherent motion diffusion-weighted imaging assessment of microvascular characteristics in the murine embryonal rhabdomyosarcoma model.

Background Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) can distinguish the false diffusion generated by microvascular blood flow from the true water molecule diffusion. Purpose To investigate the correlation between IVIM-DWI parameters and angiogenic markers such as the microvessel density and vascular endothelial growth factor (VEGF) expression in the murine embryonal rhabdomyosarcoma model. Material and Methods The murine embryonal rhabdomyosarcoma model was produced by subcutaneously injecting 107 human embryonal rhabdomyosarcoma cells into the right back of nude mice. The apparent diffusion coefficient (ADC), pseudo-diffusion coefficient (D*), true diffusion coefficient (D), and perfusion fraction (f) were obtained from 22 mice models using IVIM-DWI with b-values of 0, 50, 100, 150, 200, 400, 600, 800, 1000, and 1200 s/mm2. The microvessel density and VEGF expression were obtained by histologic examination. We then compared the correlation between IVIM-DWI parameters and microvessel density and VEGF expression. Results The average ADC, D*, D, and f values were 1.05 ± 0.27 × 10−3 mm2/s, 6.19 ± 1.78 × 10−3 mm2/s, 0.69 ± 0.09 ×10−3 mm2/s, and 17.68 ± 8.41 (%), respectively. There was moderate positive correlation between D* value and microvessel density and VEGF expression (r = 0.484, P = 0.023; r = 0.511, P = 0.015). However, there was no significant correlation between ADC, D, and f values and microvessel density and VEGF expression. Conclusion The D* value from IVIM-DWI may be used to evaluate tumor angiogenesis in the murine embryonal rhabdomyosarcoma model.

Histological Grade of Meningioma: Prediction by Intravoxel Incoherent Motion Histogram Parameters

To evaluate the usefulness of intravoxel incoherent motion (IVIM) histogram analysis for differentiating low-grade meningiomas (LGMs) and high-grade meningiomas (HGMs). Fifty-nine patients with pathologically confirmed meningiomas (45 LGMs and 14 HGMs) underwent IVIM MR imaging. Maps of IVIM parameters (perfusion fraction, f; true diffusion coefficient, D; and pseudo diffusion coefficient, D*), as well as of the apparent diffusion coefficient (ADC), were generated. Histogram analysis was performed using parametric values from all voxels in regions-of-interest manually drawn to encompass the whole tumor. The histogram results of ADC and IVIM parameters were compared using the Mann-Whitney U test. Area under the receiver operating characteristic curve (AUC) values were generated to evaluate how well each parameter could differentiate LGMs from HGMs. Spearman's rank correlation coefficients were used to evaluate correlations between histogram parameters and Ki-67 expression. Compared to LGM, HGM showed significantly higher standard deviation (SD), variance, and coefficient of variation (CV) of ADC (p< 0.006-0.028; AUC, 0.693-0.748), D (p< 0.004-0.032; AUC, 0.670-0.752), and significantly higher CV of f (p< 0.005-0.024; AUC = 0.737). Means and percentiles of ADC and IVIM parameters did not differ significantly between LGM and HGM. Significant positive correlations were identified between Ki-67 and histogram parameters of ADC (SD, variance, kurtosis, skewness, and CV) and D (SD, variance, kurtosis, and CV), whereas no significant correlation with Ki-67 was shown for mean or percentiles of ADC and IVIM parameters. Heterogeneity histogram parameters of ADC, D, and f may be useful for differentiating LGMs from HGMs.

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

Intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) parameters may reflect perfusion and diffusion changes in hepatic sinusoidal obstruction syndrome (SOS). To investigate the feasibility of IVIM-DWI in the noninvasive assessment of hepatic SOS in an experimental rat model. Animal study. 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. 3T scanner, IVIM-DWI using nine b values (0-800 sec/mm2 ). 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. 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. 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). IVIM-DWI may be useful in the diagnosis and severity assessment of hepatic SOS. 2 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:81-89.

Glioma grading and IDH1 mutational status: assessment by intravoxel incoherent motion MRI

To assess the diagnostic performance of intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) in differentiating high-grade gliomas (HGGs) from low-grade gliomas (LGGs), and predicting the isocitrate dehydrogenase 1 (IDH1) mutational status. IVIM imaging was performed preoperatively in 42 patients with gliomas using 10 b-values (0-1,200 s/mm2) in a 3 T MRI machine. The perfusion fraction (f), true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and apparent diffusion coefficient (ADC) were calculated within the tumours and in the contralateral normal white matter, and the values were compared between the HGGs and LGGs, and between IDH1 wild-type and mutated-type gliomas. In addition, the receiver operating characteristic (ROC) was also analysed. When compared to LGGs, HGGs had lower ADC (0.989×10-3 versus 1.243×10-3 mm2/s, p<0.001), smaller D (0.849×10-3 versus 1.062×10-3 mm2/s, p=0.001), larger D* (9.731×10-3 versus 5.442×10-3 mm2/s, p=0.006), and bigger f-values (0.204 versus 0.130, p<0.001) within the tumours. The area under the receiver operating characteristic (ROC) curve (AUC) was 0.937, 0.898, 0.770, and 0.838, respectively. Among the LGGs, tumours with the IDH1 mutation had a higher ADC (1.286×10-3 mm2/s), when compared to the wild-type IDH1 (1.122×10-3 mm2/s, p=0.003), with an AUC of 0.936. In HGGs, tumours with the IDH1 mutation had higher ADC (1.056×1010-3 versus 0.946×10-3 mm2/s, p=0.030), smaller D* (6.204×10-3 versus 11.999×10-3 mm2/s, p=0.023) and smaller f-values (0.143 versus 0.244, p<0.001), with an AUC of 0.766, 0.841 and 0.992, respectively. Glioma grading can be differentiated and IDH1 mutational status can be predicted using IVIM.

Noninvasive Magnetic Resonance Imaging Models for Staging Hepatic Fibrosis and Grading Inflammatory Activity in Patients with Chronic Hepatitis B

Background: In patients with chronic hepatitis B (CHB), the hepatic fibrosis (HF) stage and inflammatory activity grade are critical indicators for therapeutic strategies and prognosis. However, patients with CHB usually show no symptoms or only present with mild abdominal distension, making it difficult to stage HF and grade inflammatory activity. Invasive liver biopsy is the current gold standard for assessing HF and inflammation, but this technique has some limitations. Magnetic resonance imaging (MRI), a noninvasive and promising technique for HF evaluation, has been increasingly adopted in such cases. Diffusion-weighted imaging (DWI) with multiple b-values, a non-contrast MRI method, has become a topic of interest in the assessment and staging of HF. This study aimed to assess the value of various diffusion parameters obtained from monoexponential, biexponential, and stretched-exponential DWI models in predicting the HF stage and inflammatory activity grade in patients with CHB. Methods: 102 patients with CHB and 30 healthy volunteers underwent prospective DWI with 13 b-values on a 3T MRI unit. The standard apparent diffusion coefficient (ADCst) was calculated using a monoexponential DWI model. The true diffusion coefficient (Dt), pseudo-diffusion coefficient (Dp), and perfusion fraction (f) were calculated using a biexponential DWI model. The distributed diffusion coefficient (DDC) and water-molecule diffusion heterogeneity index (α) were calculated using a stretched-exponential DWI model. The Kruskal-Wallis H test, Mann-Whitney U test, and receiver operating characteristic (ROC) analysis were performed for all of the DWI parameters. Findings: Patients with significant fibrosis (≥F2) had lower hepatic ADCst, Dt and DDC values than those without or with early fibrosis (≤F1) and healthy volunteers (all P 0.05). Interpretation: Dt and DDC are promising indicators and outperform ADCst for diagnosing significant fibrosis and advanced fibrosis. While both Dt and DDC have similar diagnostic performance compared with ADCst in inflammatory activity grading in patients with CHB. Funding: This research was supported by the National Key R&D Program of China (2017YFE0103600), National Natural Science Foundation of China (81720108021, 81772009, 81601466, 81641168, 31470047), Scientific and Technological Research Project of Henan Province (182102310162). Declaration of Interest: F.F. disclosed no relevant relationships. X.L disclosed no relevant relationships. Y.L. disclosed no relevant relationships C.C. disclosed no relevant relationships. Y.B. disclosed no relevant relationships. J.S. disclosed no relevant relationships. D.S. disclosed no relevant relationships. J.T. disclosed no relevant relationships M.W. disclosed no relevant relationships. Ethical Approval: This prospective study was approved by the institutional review board, and informed consent was obtained from all participants.

Quantitative evaluation of intravoxel incoherent motion diffusion-weighted imaging and three-dimensional arterial spin labeling in Ki-67 labeling index and grading of brain gliomas

Objective: To investigate the value of multiple parameters derived from intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and three-dimensional arterial spin labeling (3D-ASL) in Ki-67 labeling index (Ki-67 LI) and grading of human brain gliomas. Methods: From December 2015 to May 2018, 45 patients of gliomas confirmed by surgical pathology in Li Huili Hospital, Ningbo Medical Center were divided into low-grade group (20 cases of WHO grade Ⅱ) and high-grade group (12 cases of WHO grade Ⅲ, 13 cases of WHO grade Ⅳ), and the Ki-67 LI of glioma was obtained by immunohistochemistry. All patients, 24 males and 21 females, aged 25-83 years, mean(53±12)years, underwent conventional magnetic resonance imaging (MRI), IVIM-DWI and 3D-ASL before operation, then measured the true water diffusion coefficient (D), microcirculation perfusion coefficient (D(*)), perfusion fraction (f) and cerebral blood flow (CBF) in the tumor solid area and the contralateral normal white matter area. Those parameters and the Ki-67 LI were compared between the low-and high-grade groups with Mann-Whitney U test. Spearman's correlation was used to analyze the correlation between the quantitative parameters and Ki-67 LI. The ROC curve was used to assess the diagnostic efficacy of parameters in the grading assessment of brain gliomas. Results: The D(0.791×10(-3)mm(2)/s) and f (0.261) of the high-grade group were lower than those of the low-grade group, whereas D(*) (4.153×10(-3) mm(2)/s), CBF(102.027 ml·min(-1)·100 g(-1)) and Ki-67 LI (0.25) were higher (P<0.05). There was a moderate negative correlation between D, f and Ki-67 LI(r=-0.513,-0.457, all P<0.05). There was no significant correlation between D(*) and Ki-67 LI (P=0.571). The area under the curve (AUC) for identifying high-and low-grade gliomas by D, D(*), f and CBF values was 0.965, 0.745, 0.842, and 0.830 respectively (all P<0.05). Conclusion: D and f can be used for quantitative prediction of Ki-67 LI. IVIM-DWI and 3D-ASL are helpful in the grading assessment of gliomas, and the diagnostic efficiency of D is the highest.

Estimating the free-space diffusion coefficient of trapped particles

We show that observing the trajectories of confined particles in a thermal equilibrium state yields an estimate on the free-space diffusion coefficient. For generic trapping potentials and interactions between particles, the estimate comes in the form of a lower bound on the true diffusion coefficient. For non-interacting particles in parabolic trapping potentials, which approximately describes many experimental situations, the estimate is asymptotically exact. This allows to determine the diffusion coefficient from an equilibrium measurement, as opposed to a direct observation of diffusion, which necessarily starts from a non-equilibrium state. We explicitly demonstrate that the estimate remains quantitatively accurate in the presence of weak interactions and non-parabolic corrections.

Clinical efficacy of simplified intravoxel incoherent motion imaging using three b-values for differentiating high- and low-grade gliomas.

In this study, we evaluated the efficacy of intravoxel incoherent motion (IVIM)-derived parameters calculated with three b-values in differentiating high-grade gliomas (HGGs) from low-grade gliomas (LGGs) by comparing those calculated with multiple b-values. Ten patients with LGG (ages 35.1±12.1 yrs; 4 males, 6 females) and 21 patients with HGG (ages 60.6±19.1 yrs; 10 males, 11 females) who underwent subsequent surgical resections were examined with both IVIM imaging and histopathological analysis. The IVIM diffusion-weighted imaging was conducted using a single-shot echo planar sequence with 13 b-factors (0, 10, 20, 30, 50, 80, 100, 200, 300, 400, 600, 800, and 1000 sec/mm2) at 3T. In the conventional IVIM analysis, the perfusion fraction (f) and true diffusion coefficient (D) were calculated by biexponential fitting model with 13 b-values. In the simplified method with the selected three b-values (0, 300, and 1000 sec/mm2), D simply corresponds to the slope of a straight line passing through two logarithmic signal intensities (SIs) at the b-values of 300 and 1000 s/mm2, and f corresponds to the difference between the intercept of this line and SI at the b-value of 0 sec/mm2. The maximum f (f-max) and minimum D (D-min) was measured in each tumor. The f-max values calculated with three b-values (12.8±5.9%) were significantly lower than those with 13 b-values (17.3±7.5%, p<0.0001), but a good correlation and agreement were observed between these sets of f-max values (r = 0.79, ICC = 0.87). In the IVIM imaging with both three and 13 b-values, the HGGs showed significantly higher f-max values compared to the LGGs (p<0.001, respectively). The D-min values calculated with three b-values (1.06±0.31 ×10−3 mm2/sec) was not different from those with 13 b-values (1.07±0.33 ×10−3 mm2/sec), and an excellent correlation and agreement were found between them (r = 0.99, ICC = 0.99). The simplified IVIM imaging using three b-values can efficiently differentiate HGGs and LGGs.

Intravoxel incoherent motion and diffusion kurtosis imaging for discriminating soft tissue sarcoma from vascular anomalies.

To investigate the feasibility of intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) and diffusion kurtosis imaging (DKI) in discriminating soft tissue sarcoma from vascular anomalies.Twenty-two patients with lower extremity soft tissue sarcoma and 15 patients with lower extremity vascular anomalies underwent IVIM-DWI and DKI. IVIM model generated true diffusion (D), perfusion fraction (f), and pseudo-diffusion coefficient (D∗). DKI model generated mean kurtosis (MK) and mean diffusion (MD). These parameters were measured by 2 radiologists separately through drawing region of interest. Intraclass correlation coefficient (ICC) was calculated to evaluate the inter-reader viability in measurement. The Mann–Whitney test was used to compare the parameters between vascular anomalies and soft tissue sarcoma. Receiver operating characteristic curves were constructed for assessing diagnostic accuracies.ICC was more than 0.8 for apparent diffusion coefficient (ADC), D, D∗, f, MK, and MD. Mean ADC, D, and MD were significantly lower in soft tissue sarcoma versus vascular anomalies (P < .05). Mean D∗ and f were not significantly different (P > .05). Soft tissue sarcoma had significantly higher MK than vascular anomalies (P < .05). Areas under curve for ADC, D, MK, and MD were 0.876, 0.885, 0.894, and 0.812, respectively.IVIM and DKI are feasible in discriminating soft tissue sarcoma from vascular anomalies.