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Intravoxel Incoherent Motion Diffusion-weighted Magnetic Resonance Imaging for Monitoring the Early Response to ZD6474 from Nasopharyngeal Carcinoma in Nude Mouse.

ABSTRACT: Early therapeutic effects of anti-angiogenic agent ZD6474 upon nasopharyngeal carcinoma (NPC) in nude mouse were monitored by using intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI). Mice bearing NPC underwent IVIM DWI at baseline and after 1, 3, and 7 days of treatment with ZD6474 or vehicle (n = 12 per group). Parameters of apparent diffusion coefficient (ADC), true diffusion coefficient (D), perfusion fraction (f), and blood pseudodiffusion coefficient (D*) at different time points were compared between the two groups or within the treated group. In the treated group, the perfusion-related parameters f and D* of the tumors decreased significantly on day 1 while the diffusion-related parameters ADC and D were significantly higher beginning on day 3 compared with the control group. The decreases in f on day 1 and D* on day 3 were moderately correlated with the smaller tumor size change on day 7. Moderate correlations were established between MVD and f and D* as well as between increased TUNEL or decreased Ki-67 index and ADC and D. This study supports that IVIM DWI is sensitive to detect the ZD6474-induced changes in NPC in nude mouse and the f parameter could predict early response to anti-angiogenic treatment.

SUBMITTER: Cui Y

PROVIDER: S-EPMC4648100 | biostudies-other | 2015

REPOSITORIES: biostudies-other

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Project description:OBJECTIVES:Diffusion-weighted imaging (DWI) and the introduction of the intravoxel incoherent motion (IVIM) model have provided a unique method for evaluating perfusion and diffusion within a tissue without the need for a contrast agent. Despite its relevance, cardiac DWI has thus far been limited by low b values because of signal loss induced by physiological motion. The goal of this study was to develop a methodology for estimating IVIM parameters of in vivo cardiac magnetic resonance imaging using an efficient DWI acquisition framework. This was achieved by investigating various acquisition strategies (principal component analysis [PCA] filtering and temporal maximum intensity projection [PCATMIP] and single trigger delay [TD]) and fitting methods. MATERIAL AND METHODS:Simulations were performed on a synthetic dataset of diffusion-weighted signal intensity (SI) to determine the fitting method that would yield IVIM parameters with the greatest accuracy. The required number of b values to correctly estimate IVIM parameters was also investigated. Breath-hold DWI scans were performed for 12 volunteers to collect several TD values during diastole. Thirteen b values ranging from 0 to 550 s/mm were used. The IVIM parameters derived using the data from all the acquired TDs (PCATMIP technique) were compared with those derived using a single acquisition performed at an optimized diastolic time point (1TD). RESULTS:The main result of this study was that PCATMIP, when combined with a fitting model that accounted for T1 and T2 relaxation, provided IVIM parameters with less variability. However, an acquisition performed with 1 optimized diastolic TD provided results that were as good as those provided using PCATMIP if the R-R variability during the acquisition was sufficiently low (± 5%). Furthermore, the use of only 9 b values (that could be acquired in 2 breath-holds), instead of 13 b values (requiring 3 breath-holds), was sufficient to determine the IVIM parameters. CONCLUSIONS:This study demonstrates that IVIM is technically feasible in vivo and reports for the first time the perfusion fraction, f, and the diffusion coefficients, D and D*, for the cardiac DWI of healthy volunteers. Motion-induced signal loss, which is the main problem associated with cardiac DWI, could be avoided with the combined use of sliding acquisition during the cardiac cycle and image postprocessing with the PCATMIP algorithm. This study provides new perspectives for perfusion imaging without a contrast agent and demonstrates that IVIM parameters can act as promising tools to further characterize microvascular abnormalities or dysfunction.

Project description:BACKGROUND:Pediatric retroperitoneal tumors in the renal bed are often large and heterogeneous, and their diagnosis based on conventional imaging alone is not possible. More advanced imaging methods, such as diffusion-weighted (DW) MRI and the use of intravoxel incoherent motion (IVIM), have the potential to provide additional biomarkers that could facilitate their noninvasive diagnosis. PURPOSE:To assess the use of an IVIM model for diagnosis of childhood malignant abdominal tumors and discrimination of benign from malignant lesions. STUDY TYPE:Retrospective. POPULATION:Forty-two pediatric patients with abdominal lesions (n?=?32 malignant, n?=?10 benign), verified by histopathology. FIELD STRENGTH/SEQUENCE:1.5T MRI system and a DW-MRI sequence with six b-values (0, 50, 100, 150, 600, 1000 s/mm2 ). ASSESSMENT:Parameter maps of apparent diffusion coefficient (ADC), and IVIM maps of slow diffusion coefficient (D), fast diffusion coefficient (D*), and perfusion fraction (f) were computed using a segmented fitting model. Histograms were constructed for whole-tumor regions of each parameter. STATISTICAL TESTS:Comparison of histogram parameters of and their diagnostic performance was determined using Kruskal-Wallis, Mann-Whitney U, and receiver-operating characteristic (ROC) analysis. RESULTS:IVIM parameters D* and f were significantly higher in neuroblastoma compared to Wilms' tumors (P < 0.05). The ROC analysis showed that the best diagnostic performance was achieved with D* 90th percentile (area under the curve [AUC]?=?0.935; P?=?0.002; cutoff value?=?32,376 × 10-6 mm2 /s) and f mean values (AUC?=?1.00; P < 0.001; cutoff value?=?14.7) in discriminating between neuroblastoma (n?=?11) and Wilms' tumors (n?=?8). Discrimination between tumor types was not possible with IVIM D or ADC parameters. Malignant tumors revealed significantly lower ADC, D, and higher D* values than in benign lesions (all P < 0.05). DATA CONCLUSION:IVIM perfusion parameters could distinguish between malignant childhood tumor types, providing potential imaging biomarkers for their diagnosis. LEVEL OF EVIDENCE:4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1475-1486.

Project description:The aim of the study was to prospectively evaluate the clinical value of intravoxel incoherent motion (IVIM)-magnetic resonance imaging (MRI) in early predicting the treatment response to neoadjuvant chemotherapy (NAC) for nasopharyngeal carcinoma (NPC). Forty-eight patients with locoregionally advanced NPC were imaged with IVIM-MRI (14 b-factors, 0-1000 s/mm2) on a 3.0-T Magnetic resonance system, at the baseline, and repeatedly at the third and 21st day after NAC started. The IVIM-derived parameters (D*, pure diffusion coefficient; f, perfusion fraction; and D, pseudodiffusion coefficient) were calculated with the Interactive Data Language version 6.3 software. The baseline parameters and their corresponding changes (Δparameter(day)) during NAC were compared using the Student t test or Mann-Whitney U test. Variation analyses of IVIM-derived parameters were tested with intraclass correlation coefficient. Receiver-operating characteristic (ROC) curve analysis was conducted to estimate the best diagnostic accuracy. Statistical analyses were performed on the SPSS 18.0 software, with a 2-tailed probability value, P < 0.05 was considered significant. Among recruited patients, 37 cases were categorized as responders and 11 cases as nonresponders after NAC completed. The intra- and interobserver intraclass correlation coefficient of IVIM-derived parameters were excellent, which ranged from 0.858 to 0.971. Compared with the baseline value, at the third and 21st day, the D value was significantly higher and the D* value significantly lower (P < 0.05, P < 0.001, respectively). In contrast, f parameter only changed slightly (P > 0.05). Compared with nonresponders, responders presented a notably lower baseline D value and higher ΔD3, ΔD21, ΔD3*, ΔD21*, and Δf21 (P < 0.05), but no significant change in Δf3 was observed (P > 0.1). The receiver-operating characteristic curve analyses indicated that the threshold of baseline D values that best predicted the responders for primary nasopharynx tumors and metastatic lymph nodes were 0.911 × 10(-3) mm2/s versus 0.951 × 10(-3) mm2/s, and their corresponding area under curve, sensitivity, and specificity were 0.714 versus 0.774, 0.658 versus 0.538, and 0.818 versus 0.944, respectively. IVIM-MRI can potentially early predict the treatment response of NAC for NPC patients. The baseline D value, and early changes in D and D value are better predictors of the chemotherapeutic responsiveness.

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Intravoxel Incoherent Motion Diffusion-weighted Magnetic Resonance Imaging for Monitoring the Early Response to ZD6474 from Nasopharyngeal Carcinoma in Nude Mouse.

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