Treatment response monitoring in patients with gastrointestinal stromal tumor using diffusion‐weighted imaging: preliminary results in comparison with positron emission tomography/computed tomography

We compared the parameters derived from diffusion‐weighted imaging (DWI) and positron emission tomography/computed tomography (PET/CT) for treatment response evaluation and response prediction in patients with gastrointestinal stromal tumor (GIST). Seven patients with histologically proven metastatic disease were enrolled. DWI and PET/CT data were collected from all patients at diagnosis and from six at follow‐up. All 37 lesions were identifiable in DWI with a sensitivity of 100%. To achieve higher accuracy, we used the apparent diffusion coefficient (ADC) of liver and background noise as thresholds for the measurement of the ADCs of lesions. Significant inverse correlations were found between ADC_{mean_thr} (ADC_mean with thresholds) and SUV_mean (mean standardized uptake value) (R² = 0.523, p < 0.001 at diagnosis, and R² = 0.916, p < 0.001 at follow‐up), between ADC_{mean_thr} and SUV_max (maximum SUV) (R² = 0.529, p < 0.001 at diagnosis, and R² = 0.761, p < 0.001 at follow‐up), between ΔADC_{mean_thr} (percentage change in ADC_{mean_thr}) and ΔSUV_mean (percentage change in SUV_mean) (R² = 0.384, p < 0.001), and between ΔADC_{mean_thr} and ΔSUV_max (percentage change in SUV_max) (R² = 0.500, p < 0.001). In lesion‐based analysis, pre‐treatment ADC_{mean_thr} outperformed SUV_mean and SUV_max in treatment response prediction, with an area under the receiver operating characteristic curve of 0.706. These results show that DWI can provide a quantitative assessment comparable with PET/CT in GIST lesion characterization, treatment response evaluation and response prediction. Copyright © 2012 John Wiley & Sons, Ltd.     

Diffusion‐weighted MRI for staging and evaluation of response in diffuse large B‐cell lymphoma: a pilot study

The aim of this study was to compare diffusion‐weighted MRI (DW‐MRI) with positron emission tomography/computed tomography (PET/CT) for the staging and evaluation of the treatment response in patients with diffuse large B‐cell lymphoma (DLBCL). Institutional review board approval was obtained for this study; all subjects gave informed consent. Twelve patients were imaged before treatment and eight of these were also imaged after two cycles of chemotherapy using both DW‐MRI and PET/CT. Up to six target lesions were selected at baseline for response assessment based on International Working Group criteria (nodes > 1.5 cm in diameter; extranodal lesions > 1 cm in diameter). For pretreatment staging, visual analysis of the numbers of nodal and extranodal lesions based on PET/CT was performed. For interim response assessment after cycle 2 of chemotherapy, residual tumor sites were assessed visually and the percentage changes in target lesion size, maximum standardized uptake value (SUV_max) and apparent diffusion coefficient (ADC) from pretreatment values were calculated. In 12 patients studied pretreatment, there were 46 nodal and 16 extranodal sites of lymphomatous involvement. Agreement between DW‐MRI and PET/CT for overall lesion detection was 97% (60/62 tumor sites; 44/46 nodal and 16/16 extranodal lesions) and, for Ann Arbor stage, it was 100%. In the eight patients who had interim assessment, five of their 49 tumor sites remained abnormal on visual analysis of both DW‐MRI and PET/CT, and there was one false positive on DW‐MRI. Of their 24 target lesions, the mean pretreatment ADC value, tumor size and SUV_max were 772 µm²/s, 21.3 cm² and 16.9 g/mL, respectively. At interim assessment of the same 24 target lesions, ADC values increased by 85%, tumor size decreased by 74% and SUV_max decreased by 83% (all p < 0.01 versus baseline). DW‐MRI provides results comparable with those of PET/CT for staging and early response assessment in patients with DLBCL. Copyright © 2014 John Wiley & Sons, Ltd.     

Comparison of different MRI sequences in lesion detection and early response evaluation of diffuse large B‐cell lymphoma – a whole‐body MRI and diffusion‐weighted imaging study

To compare different MRI sequences for the detection of lesions and the evaluation of response to chemotherapy in patients with diffuse large B‐cell lymphoma (DLBCL), 18 patients with histology‐confirmed DLBCL underwent 3‐T MRI scanning prior to and 1 week after chemotherapy. The MRI sequences included T₁‐weighted pre‐ and post‐contrast, T₂‐weighted with and without fat suppression, and a single‐shot echo‐planar diffusion‐weighted imaging (DWI) with two b values (0 and 800 s/mm²). Conventional MRI sequence comparisons were performed using the contrast ratio between tumor and normal vertebral body instead of signal intensity. The apparent diffusion coefficient (ADC) of the tumor was measured directly on the parametric ADC map. The tumor volume was used as a reference for the evaluation of chemotherapy response. The mean tumor volume was 374 mL at baseline, and decreased by 65% 1 week after chemotherapy (p < 0.01). The T₂‐weighted image with fat suppression showed a significantly higher contrast ratio compared with images from all other conventional MRI sequences, both before and after treatment (p < 0.01, respectively). The contrast ratio of the T₂‐weighted image with fat suppression decreased significantly (p < 0.01), and that of the T₁‐weighted pre‐contrast image increased significantly (p < 0.01), after treatment. However, there was no correlation between the change in contrast ratio and tumor volume. The mean ADC value was 0.68 × 10^–3 mm²/s at baseline; it increased by 89% after chemotherapy (p < 0.001), and the change in ADC value correlated with the change in tumor volume (r = 0.66, p < 0.01). The baseline ADC value also correlated inversely with the percentage change in ADC after treatment (r = ?0.62, p < 0.01). In conclusion, this study indicates that T₂‐weighted imaging with fat suppression is the best conventional sequence for the detection of lesions and evaluation of the efficacy of chemotherapy in DLBCL. DWI with ADC mapping is an imaging modality with both diagnostic and prognostic value that could complement conventional MRI. Copyright © 2013 John Wiley & Sons, Ltd.     

Predictive significance of standardized uptake value parameters of FDG-PET in patients with non-small cell lung carcinoma

¹⁸F-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is widely used to diagnose and stage non-small cell lung cancer (NSCLC). The aim of this retrospective study was to evaluate the predictive ability of different FDG standardized uptake values (SUVs) in 74 patients with newly diagnosed NSCLC. ¹⁸F-FDG PET/CT scans were performed and different SUV parameters (SUV_max, SUV_avg, SUV_T/L, and SUV_T/A) obtained, and their relationship with clinical characteristics were investigated. Meanwhile, correlation and multiple stepwise regression analyses were performed to determine the primary predictor of SUVs for NSCLC. Age, gender, and tumor size significantly affected SUV parameters. The mean SUVs of squamous cell carcinoma were higher than those of adenocarcinoma. Poorly differentiated tumors exhibited higher SUVs than well-differentiated ones. Further analyses based on the pathologic type revealed that the SUV_max, SUV_avg, and SUV_T/L of poorly differentiated adenocarcinoma tumors were higher than those of moderately or well-differentiated tumors. Among these four SUV parameters, SUV_T/L was the primary predictor for tumor differentiation. However, in adenocarcinoma, SUV_max was the determining factor for tumor differentiation. Our results showed that these four SUV parameters had predictive significance related to NSCLC tumor differentiation; SUV_T/L appeared to be most useful overall, but SUV_max was the best index for adenocarcinoma tumor differentiation.     

DCE and DW-MRI monitoring of vascular disruption following VEGF-Trap treatment of a rat glioma model

Vascular‐targeted therapies have shown promise as adjuvant cancer treatment. As these agents undergo clinical evaluation, sensitive imaging biomarkers are needed to assess drug target interaction and treatment response. In this study, dynamic contrast enhanced MRI (DCE‐MRI) and diffusion‐weighted MRI (DW‐MRI) were evaluated for detecting response of intracerebral 9 L gliosarcomas to the antivascular agent VEGF‐Trap, a fusion protein designed to bind all forms of Vascular Endothelial Growth Factor‐A (VEGF‐A) and Placental Growth Factor (PGF). Rats with 9 L tumors were treated twice weekly for two weeks with vehicle or VEGF‐Trap. DCE‐ and DW‐MRI were performed one day prior to treatment initiation and one day following each administered dose. Kinetic parameters (K^trans, volume transfer constant; k_ep, efflux rate constant from extravascular/extracellular space to plasma; and v_p, blood plasma volume fraction) and the apparent diffusion coefficient (ADC) over the tumor volumes were compared between groups. A significant decrease in kinetic parameters was observed 24 hours following the first dose of VEGF‐Trap in treated versus control animals (p < 0.05) and was accompanied by a decline in ADC values. In addition to the significant hemodynamic effect, VEGF‐Trap treated animals exhibited significantly longer tumor doubling times (p < 0.05) compared to the controls. Histological findings were found to support imaging response metrics. In conclusion, kinetic MRI parameters and change in ADC have been found to serve as sensitive and early biomarkers of VEGF‐Trap anti‐vascular targeted therapy. Copyright © 2011 John Wiley & Sons, Ltd.     

High‐field (11.75T) multimodal MR imaging of exercising hindlimb mouse muscles using a non‐invasive combined stimulation and force measurement device

We have designed and constructed an experimental set‐up allowing electrical stimulation of hindlimb mouse muscles and the corresponding force measurements at high‐field (11.75T). We performed high‐resolution multimodal MRI (including T₂‐weighted imaging, angiography and diffusion) and analysed the corresponding MRI changes in response to a stimulation protocol. Mice were tested twice over a 1‐week period to investigate the reliability of mechanical measurements and T₂ changes associated with the stimulation protocol. Additionally, angiographic images were obtained before and immediately after the stimulation protocol. Finally, multislice diffusion imaging was performed before, during and immediately after the stimulation session. Apparent diffusion coefficient (ADC) maps were calculated on the basis of diffusion weighted images (DWI). Both force production and T₂ values were highly reproducible as illustrated by the low coefficient of variation (<8%) and high intraclass correlation coefficient (≥0.75) values. Maximum intensity projection angiographic images clearly showed a strong vascular effect resulting from the stimulation protocol. Although a motion sensitive imaging sequence was used (echo planar imaging) and in spite of the strong muscle contractions, motion artifacts were minimal for DWI recorded under exercising conditions, thereby underlining the robustness of the measurements. Mean ADC values increased under exercising conditions and were higher during the recovery period as compared with the corresponding control values. The proposed experimental approach demonstrates accurate high‐field multimodal MRI muscle investigations at a preclinical level which is of interest for monitoring the severity and/or the progression of neuromuscular diseases but also for assessing the efficacy of potential therapeutic interventions. Copyright © 2014 John Wiley & Sons, Ltd.     

Time‐dependent diffusion MRI as a probe of microstructural changes in a mouse model of Duchenne muscular dystrophy

Dystrophic muscles show a high variability of fibre sizes and altered sarcolemmal integrity, which are typically assessed by histology. Time‐dependent diffusion MRI is sensitive to tissue microstructure and its investigation through age‐related changes in dystrophic and healthy muscles may help the understanding of the onset and progression of Duchenne muscular dystrophy (DMD). We investigated the capability of time‐dependent diffusion MRI to quantify age and disease‐related changes in hind‐limb muscle microstructure between dystrophic (mdx) and wild‐type (WT) mice of three age groups (7.5, 22 and 44 weeks). Diffusion time‐dependent apparent diffusion coefficients (ADCs) of the gastrocnemius and tibialis anterior muscles were determined versus age and diffusion‐gradient orientation at six diffusion times (Δ; range: 25–350 ms). Mean muscle ADCs were compared between groups and ages, and correlated with T₂, using Student's t test, one‐way analysis of variance and Pearson correlation, respectively. Muscle fibre sizes and sarcolemmal integrity were evaluated by histology and compared with diffusion measurements. Hind‐limb muscle ADC showed characteristic restricted diffusion behaviour in both mdx and WT animals with decreasing ADC values at longer Δ. Significant differences in ADC were observed at long Δ values (≥ 250 ms; p < 0.05, comparison between groups; p < 0.01, comparison between ages) with ADC increased by 5–15% in dystrophic muscles, indicative of reduced diffusion restriction. No significant correlation was found between T₂ and ADC. Additionally, muscle fibre size distributions showed higher variability and lower mean fibre size in mdx than WT animals (p < 0.001). The extensive Evans Blue Dye uptake shown in dystrophic muscles revealed substantial sarcolemmal damage, suggesting diffusion measurements as more consistent with altered permeability rather than changes in muscle fibre sizes. This study shows the potential of diffusion MRI to non‐invasively discriminate between dystrophic and healthy muscles with enhanced sensitivity when using long Δ.     

Correlation of tumor characteristics derived from DCE‐MRI and DW‐MRI with histology in murine models of breast cancer

The purpose of this work was to determine the relationship between the apparent diffusion coefficient (ADC, from diffusion‐weighted (DW) MRI), the extravascular, extracellular volume fraction (v_e, from dynamic contrast‐enhanced (DCE) MRI), and histological measurement of the extracellular space fraction. Athymic nude mice were injected with either human epidermal growth factor receptor 2 positive (HER2+) BT474 (n = 15) or triple negative MDA‐MB‐231 (n = 20) breast cancer cells, treated with either Herceptin (n = 8), Abraxane (low dose n = 7, high dose n = 6), or saline (n = 7 for each cell line), and imaged using DW‐ and DCE‐MRI before, during, and after treatment. After the final imaging acquisition, the tissue was resected and evaluated by histological analysis. H&E‐stained central slices were scanned using a digital brightfield microscope and evaluated with thresholding techniques to calculate the extracellular space. For both BT474 and MDA‐MB‐231, the median ADC of the central slice exhibited a significantly positive correlation with the corresponding central slice extracellular space as measured by H&E (p = 0.03, p < 0.01, respectively). Median v_e calculated from the central slice showed differing results between the two cell lines. For BT474, a significant correlation between v_e and extracellular space was calculated (p = 0.02), while MDA‐MB‐231 tumors did not demonstrate a significant correlation (p = 0.64). Additionally, there was no correlation discovered between ADC and v_e with either whole tumor analysis or central slice analysis (p > 0.05). While ADC correlates well with the histologically determined fraction of extracellular space, these data add to the growing body of literature that suggests that v_e derived from DCE‐MRI is not a reliable biomarker of extracellular space for a range of physiological conditions. Copyright © 2015 John Wiley & Sons, Ltd.     

Diffusion‐weighted imaging of the abdomen: Impact of b‐values on texture analysis features

The purpose of this work was to systematically assess the impact of the b‐value on texture analysis in MR diffusion‐weighted imaging (DWI) of the abdomen. In eight healthy male volunteers, echo‐planar DWI sequences at 16 b‐values ranging between 0 and 1000 s/mm² were acquired at 3 T. Three different apparent diffusion coefficient (ADC) maps were computed (0, 750/100, 390, 750 s/mm²/all b‐values). Texture analysis of rectangular regions of interest in the liver, kidney, spleen, pancreas, paraspinal muscle and subcutaneous fat was performed on DW images and the ADC maps, applying 19 features computed from the histogram, grey‐level co‐occurrence matrix (GLCM) and grey‐level run‐length matrix (GLRLM). Correlations between b‐values and texture features were tested with a linear and an exponential model; the best fit was determined by the smallest sum of squared residuals. Differences between the ADC maps were assessed with an analysis of variance. A Bonferroni‐corrected p‐value less than 0.008 (=0.05/6) was considered statistically significant. Most GLCM and GLRLM‐derived texture features (12–18 per organ) showed significant correlations with the b‐value. Four texture features correlated significantly with changing b‐values in all organs (p < 0.008). Correlation coefficients varied between 0.7 and 1.0. The best fit varied across different structures, with fat exhibiting mostly exponential (17 features), muscle mostly linear (12 features) and the parenchymatous organs mixed feature alterations. Two GLCM features showed significant variability in the different ADC maps. Several texture features vary systematically in healthy tissues at different b‐values, which needs to be taken into account if DWI data with different b‐values are analyzed. Histogram and GLRLM‐derived texture features are stable on ADC maps computed from different b‐values.     

Prediction of pathologic response to neoadjuvant chemotherapy in patients with breast cancer using diffusion‐weighted imaging and MRS

The aim of this study was to determine whether tumor size, MRS parameters and apparent diffusion coefficient (ADC) measurements could be applied to predict pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC). Ninety patients with breast cancer (median size, 4.5 cm; range, 1.6–9.5 cm) were evaluated with single‐voxel ¹H MRS and dynamic contrast‐enhanced MRI. Diffusion‐weighted imaging was performed in 41 of these patients using a 1.5‐T scanner before and after completion of NAC. Pre‐ and post‐treatment measurements and changes in tumor size, MRS parameters [absolute and normalized total choline‐containing compound (tCho) integral and tCho signal‐to‐noise ratio (SNR)] and ADCs in pCR versus non‐pCR were compared using the nonparametric Mann–Whitney test. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic performance of each parameter. After NAC, 30 patients (33%) showed pCR and 60 (67%) showed non‐pCR. At pretreatment, ADC was the only significant parameter in differentiating between pCR and non‐pCR [(0.83 ± 0.05) × 10^–3 versus (0.97 ± 0.14) × 10^–3 mm²/s] (p = 0.014). Post‐treatment measurements after completion of NAC and changes in tumor size (both p < 0.001), MRS parameters (p = 0.027 and p = 0.020 for absolute tCho integral, p = 0.036 and p = 0.023 for normalized tCho integral, and p = 0.032 and p = 0.061 for tCho SNR) and ADC (p = 0.003 and p < 0.001) were significantly different between the pCR and non‐pCR groups, except for changes in tCho SNR. In ROC analysis, the areas under the ROC curve (AUCs) of 0.63–0.73 were obtained for tumor size and MRS parameters. AUCs for pre‐ and post‐treatment ADC and changes in ADC were 0.75, 0.80 and 0.96, respectively. The optimal cut‐off of the percentage change in ADC for predicting pCR was 40.7%, yielding 100% sensitivity and 91% specificity. Patients with pCR showed significantly lower pretreatment ADCs than those with non‐pCR. The change in ADC after NAC was the most accurate predictor of pCR. Copyright © 2012 John Wiley & Sons, Ltd.     

DWI、ADC图对急性脑梗塞诊断的应用及病理生理基础

目的:探讨磁共振弥散加权成像(DW-MRI)及表观弥散系数图(ADC mapping)在急性脑梗塞诊断中的应用价值及病理生理基础。方法:应用单次激发平面回波三向同性弥散加权MRI和常规MRI对21例脑梗塞患者进行检查。其中超急性期8例,急性期13例,测定病灶平均表观弥散系数(ADC)值、相对表现弥散系数(rADC)及中心边缘ADC值。结果:超急性期8例均在DWI及ADC图上显示出缺血灶,但其在CT及T₂WI上表现正常。超急性、急性期脑梗塞在DWI上表现为高信号,其ADC值明显低于对侧相应区域,平均ADC值为(0.698±0.104)×10^-3mm²/s vs(0.990±0.161)×10^-3mm²/s(P<0.01),21例超急性、急性期病灶ADC值出现梯度征。结论:三向同性DWI及ADC图对急性脑梗塞,尤其是超急性脑梗塞较常规MRI及CT具有更高的敏感性,能快速、准确地诊断超急性、急性脑硬塞,并能反映缺血半暗带等相应的病理生理变化。     

Correlation of Choline/Creatine and Apparent Diffusion Coefficient values with the prognostic parameters of Head and Neck Squamous Cell Carcinoma

The aim of this study was to measure choline/creatine (Ch/Cr) levels through ¹H‐MRS and apparent diffusion coefficient (ADC) values through diffusion‐weighted MRI, and to correlate these values with the prognostic parameters of head and neck squamous cell carcinoma (HNSCC). The institutional review board approved this study and informed written consent was obtained from all study participants. A prospective study of 43 patients (31 men and 12 women; mean age, 65 years) with HNSCC was conducted. Single‐voxel ¹H‐MRS was performed at the tumor or metastatic cervical lymph node with point‐resolved spectroscopy (PRESS) at TE = 135 ms. Diffusion‐weighted MR images with b values of 0, 500 and 1000 s/mm² and contrast MRI of the head and neck were performed. The Ch/Cr levels and ADC values of HNSCC were calculated. The gross tumor volume (GTV) was also calculated. The degree of tumor differentiation was determined through pathological examination. The HNSCC Ch/Cr level was negatively correlated with the ADC value (r = ?0.662, p = 0.001). There was a significant difference in the Ch/Cr and ADC values at different degrees of tumor differentiation (p = 0.003 and p = 0.001) and with different GTVs (p = 0.122 and p = 0.001). The following prognostic parameter categories were used: (i) poorly differentiated and undifferentiated versus well differentiated to moderately differentiated; and (ii) HNSCC with GTV < 30 cm³ versus GTV > 30 cm³. The cut‐off values for Cho/Cr and ADC for each category were 1.83, 0.95 and 1.94, 0.99, respectively, and the areas under the curve were 0.771, 0.967 and 0.726, 0.795, respectively, for each category. We conclude that the Ch/Cr levels determined using ¹H‐MRS and the ADC values are well correlated with several prognostic parameters of HNSCC. Copyright © 2016 John Wiley & Sons, Ltd.     

MRI of neonatal necrotizing enterocolitis in a rodent model

Neonatal necrotizing enterocolitis (NEC) is a poorly understood life‐threatening illness afflicting premature infants. Research is hampered by the absence of a suitable method to monitor disease progression noninvasively. The primary goal of this research was to test in vivo MRI methods for the noninvasive early detection and staging of inflammation in the ileum of an infant rat model of NEC. Neonatal rats were delivered by cesarean section at embryonic stage of day 20 after the beginning of pregnancy and stressed with formula feeding, hypoxia and bacterial colonization to induce NEC. Naturally born and dam‐fed neonatal rats were used as healthy controls. In vivo MRI studies were performed using a Bruker 9.4‐T scanner to obtain high‐resolution anatomical MR images using both gradient echo and spin echo sequences, pixel‐by‐pixel T₂ maps using a multi‐slice–multi‐echo sequence, and maps of the apparent diffusion coefficient (ADC) of water using a spin echo sequence, to assess the degree of ileal damage. Pups were sacrificed at the end of the MRI experiment on day 2 or 4 for histology. T₂ measured by MRI was increased significantly in the ileal regions of pups with NEC by histology (106.3 ± 6.1 ms) compared with experimentally stressed pups without NEC (85.2 ± 6.8 ms) and nonstressed, control rat pups (64.9 ± 2.3 ms). ADC values measured by diffusion‐weighted MRI were also increased in the ileal regions of pups with NEC by histology [(1.98 ± 0.15) × 10^–3 mm²/s] compared with experimentally stressed pups without NEC [(1.43 ± 0.16) × 10^–3 mm²/s] and nonstressed control pups [(1.10 ± 0.06) × 10^–3 mm²/s]. Both T₂ and ADC values between these groups were found to be significantly different (p < 0.03). The correlation of MRI results with histologic images of the excised ileal tissue samples strongly suggests that MRI can noninvasively identify NEC and assess intestinal injury prior to clinical symptoms in a physiologic rat pup model of NEC. © 2013 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd.     

Imaging quality of PROPELLER diffusion‐weighted MR imaging and its diagnostic performance in distinguishing pleomorphic adenomas from Warthin tumors of the parotid gland

The aim of this study was to evaluate the imaging quality and diagnostic performance of fast spin echo diffusion‐weighted imaging with periodically rotated overlapping parallel lines with enhanced reconstruction (FSE‐PROP‐DWI) in distinguishing parotid pleomorphic adenoma (PMA) from Warthin tumor (WT). This retrospective study enrolled 44 parotid gland tumors from 34 patients, including 15 PMAs and 29 WTs with waived written informed consent. All participants underwent 1.5 T diffusion‐weighted imaging including FSE‐PROP‐DWI and single‐shot echo‐planar diffusion‐weighted imaging (SS‐EP‐DWI). After imaging resizing and registration among T2WI, FSE‐PROP‐DWI and SS‐EP‐DWI, imaging distortion was quantitatively analyzed by using the Dice coefficient. Signal‐to‐noise ratio and contrast‐to‐noise ratio were qualitatively evaluated. The mean apparent diffusion coefficient (ADC) of parotid gland tumors was calculated. Wilcoxon signed‐rank test was used for paired comparison between FSE‐PROP‐DWI versus SS‐EP‐DWI. Mann–Whitney U test was used for independent group comparison between PMAs versus WTs. Diagnostic performance was evaluated by receiver operating characteristics curve analysis. P < 0.05 was considered statistically significant. The Dice coefficient was statistically significantly higher on FSE‐PROP‐DWI than SS‐EP‐DWI for both tumors (P < 0.005). Mean ADC was statistically significantly higher in PMAs than WTs on both FSE‐PROP‐DWI and SS‐EP‐DWI (P < 0.005). FSE‐PROP‐DWI and SS‐EP‐DWI successfully distinguished PMAs from WTs with an AUC of 0.880 and 0.945, respectively (P < 0.05). Sensitivity, specificity, positive predictive value, negative predictive value and accuracy in diagnosing PMAs were 100%, 69.0%, 62.5%, 100% and 79.5% for FSE‐PROP‐DWI, and 100%, 82.8%, 75%, 100% and 88.6% for SS‐EP‐DWI, respectively. FSE‐PROP‐DWI is useful to distinguish parotid PMAs from WTs with less distortion of tumors but lower AUC than SS‐EP‐DWI.     

Generative adversarial network‐based super‐resolution of diffusion‐weighted imaging: Application to tumour radiomics in breast cancer

Diffusion‐weighted imaging (DWI) is increasingly used to guide the clinical management of patients with breast tumours. However, accurate tumour characterization with DWI and the corresponding apparent diffusion coefficient (ADC) maps are challenging due to their limited resolution. This study aimed to produce super‐resolution (SR) ADC images and to assess the clinical utility of these SR images by performing a radiomic analysis for predicting the histologic grade and Ki‐67 expression status of breast cancer. To this end, 322 samples of dynamic enhanced magnetic resonance imaging (DCE‐MRI) and the corresponding DWI data were collected. A SR generative adversarial (SRGAN) and an enhanced deep SR (EDSR) network along with the bicubic interpolation were utilized to generate SR‐ADC images from which radiomic features were extracted. The dataset was randomly separated into a development dataset (n = 222) to establish a deep SR model using DCE‐MRI and a validation dataset (n = 100) to improve the resolution of ADC images. This random separation of datasets was performed 10 times, and the results were averaged. The EDSR method was significantly better than the SRGAN and bicubic methods in terms of objective quality criteria. Univariate and multivariate predictive models of radiomic features were established to determine the area under the receiver operating characteristic curve (AUC). Individual features from the tumour SR‐ADC images showed a higher performance with the EDSR and SRGAN methods than with the bicubic method and the original images. Multivariate analysis of the collective radiomics showed that the EDSR‐ and SRGAN‐based SR‐ADC images performed better than the bicubic method and original images in predicting either Ki‐67 expression levels (AUCs of 0.818 and 0.801, respectively) or the tumour grade (AUCs of 0.826 and 0.828, respectively). This work demonstrates that in addition to improving the resolution of ADC images, deep SR networks can also improve tumour image‐based diagnosis in breast cancer.     

A multi‐Gaussian model for apparent diffusion coefficient histogram analysis of Wilms’ tumour subtype and response to chemotherapy

Wilms’ tumours (WTs) are large heterogeneous tumours, which typically consist of a mixture of histological cell types, together with regions of chemotherapy‐induced regressive change and necrosis. The predominant cell type in a WT is assessed histologically following nephrectomy, and used to assess the tumour subtype and potential risk. The purpose of this study was to develop a mathematical model to identify subregions within WTs with distinct cellular environments in vivo, determined using apparent diffusion coefficient (ADC) values from diffusion‐weighted imaging (DWI). We recorded the WT subtype from the histopathology of 32 tumours resected in patients who received DWI prior to surgery after pre‐operative chemotherapy had been administered. In 23 of these tumours, DWI data were also available prior to chemotherapy. Histograms of ADC values were analysed using a multi‐Gaussian model fitting procedure, which identified ‘subpopulations’ with distinct cellular environments within the tumour volume. The mean and lower quartile ADC values of the predominant viable tissue subpopulation (ADC_1MEAN, ADC_1LQ), together with the same parameters from the entire tumour volume (ADC_0MEAN, ADC_0LQ), were tested as predictors of WT subtype. ADC_1LQ from the multi‐Gaussian model was the most effective parameter for the stratification of WT subtype, with significantly lower values observed in high‐risk blastemal‐type WTs compared with intermediate‐risk stromal, regressive and mixed‐type WTs (p < 0.05). No significant difference in ADC_1LQ was found between blastemal‐type and intermediate‐risk epithelial‐type WTs. The predominant viable tissue subpopulation in every stromal‐type WT underwent a positive shift in ADC_1MEAN after chemotherapy. Our results suggest that our multi‐Gaussian model is a useful tool for differentiating distinct cellular regions within WTs, which helps to identify the predominant histological cell type in the tumour in vivo. This shows potential for improving the risk‐based stratification of patients at an early stage, and for guiding biopsies to target the most malignant part of the tumour. Copyright © 2015 John Wiley & Sons, Ltd.     

The Value of 18F-FDG PET/CT in Evaluating Disease Severity and Prognosis in Idiopathic Pulmonary Fibrosis Patients

BackgroundSeveral parameters are useful for assessing disease severity in idiopathic pulmonary fibrosis (IPF); however, the role of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) is not well-defined. We aimed to evaluate the value of ¹⁸F-FDG PET/CT for assessing disease severity and prognosis in IPF patients.MethodsClinical data of 89 IPF patients (mean age: 68.1 years, male: 94%) who underwent ¹⁸F-FDG PET/CT for evaluation of lung nodules or cancer staging were retrospectively reviewed. Mean and maximal standardized uptake values (SUV_mean, SUV_max, respectively) were measured in the fibrotic area. Adjusted SUV, including SUV ratio (SUVR, defined as SUV_max-to-liver SUV_mean ratio), tissue fraction-corrected SUV_mean (SUV_meanTF), and SUVR (SUVR_TF), and tissue-to-blood ratio (SUV_max/SUV_mean venous; TBR_blood) were obtained. Death was defined as the primary outcome, and associations between other clinical parameters (lung function, exercise capacity, C-reactive protein [CRP] level) were also investigated.ResultsAll SUV parameters were inversely correlated with the forced vital capacity, diffusing capacity for carbon monoxide, and positively correlated with CRP level and the gender-age-physiology index. The SUV_mean, SUV_max, and SUV_meanTF were associated with changes in lung function at six months. The SUVR (hazard ratio [HR], 1.738; 95% confidence interval [CI], 1.011–2.991), SUVR_TF (HR, 1.441; 95% CI, 1.000–2.098), and TBR_blood (HR, 1.377; 95% CI, 1.038–1.827) were significant predictors for mortality in patients with IPF in the univariate analysis, but not in the multivariate analysis.Conclusion¹⁸F-FDG PET/CT may provide additional information on the disease severity and prognosis in IPF patients, and the SUVR may be superior to other SUV parameters.     

Response of HT29 colorectal xenograft model to cediranib assessed with 18F‐fluoromisonidazole positron emission tomography,dynamic contrast‐enhanced and diffusion‐weighted MRI

Cediranib is a small‐molecule pan‐vascular endothelial growth factor receptor inhibitor. The tumor response to short‐term cediranib treatment was studied using dynamic contrast‐enhanced and diffusion‐weighted MRI at 7 T, as well as ¹⁸F‐fluoromisonidazole positron emission tomography and histological markers. Rats bearing subcutaneous HT29 human colorectal tumors were imaged at baseline; they then received three doses of cediranib (3 mg/kg per dose daily) or vehicle (dosed daily), with follow‐up imaging performed 2 h after the final cediranib or vehicle dose. Tumors were excised and evaluated for the perfusion marker Hoechst 33342, the endothelial cell marker CD31, smooth muscle actin, intercapillary distance and tumor necrosis. Dynamic contrast‐enhanced MRI‐derived parameters decreased significantly in cediranib‐treated tumors relative to pretreatment values [the muscle‐normalized initial area under the gadolinium concentration curve decreased by 48% (p = 0.002), the enhancing fraction by 43% (p = 0.003) and K^trans by 57% (p = 0.003)], but remained unchanged in controls. No change between the pre‐ and post‐treatment tumor apparent diffusion coefficients in either the cediranib‐ or vehicle‐treated group was observed over the course of this study. The ¹⁸F‐fluoromisonidazole mean standardized uptake value decreased by 33% (p = 0.008) in the cediranib group, but showed no significant change in the control group. Histological analysis showed that the number of CD31‐positive vessels (59 per mm²), the fraction of smooth muscle actin‐positive vessels (80–87%) and the intercapillary distance (0.17 mm) were similar in cediranib‐ and vehicle‐treated groups. The fraction of perfused blood vessels in cediranib‐treated tumors (81 ± 7%) was lower than that in vehicle controls (91 ± 3%, p = 0.02). The necrotic fraction was slightly higher in cediranib‐treated rats (34 ± 12%) than in controls (26 ± 10%, p = 0.23). These findings suggest that short‐term treatment with cediranib causes a decrease in tumor perfusion/permeability across the tumor cross‐section, but changes in vascular morphology, vessel density or tumor cellularity are not manifested at this early time point. Copyright © 2012 John Wiley & Sons, Ltd.     

Diffusion‐weighted MRI of breast lesions: a prospective clinical investigation of the quantitative imaging biomarker characteristics of reproducibility,repeatability, and diagnostic accuracy

Diffusion‐weighted MRI (DWI) provides insights into tissue microstructure by visualization and quantification of water diffusivity. Quantitative evaluation of the apparent diffusion coefficient (ADC) obtained from DWI has been proven helpful for differentiating between malignant and benign breast lesions, for cancer subtyping in breast cancer patients, and for prediction of response to neoadjuvant chemotherapy. However, to further establish DWI of breast lesions it is important to evaluate the quantitative imaging biomarker (QIB) characteristics of reproducibility, repeatability, and diagnostic accuracy. In this intra‐individual prospective clinical study 40 consecutive patients with suspicious findings, scheduled for biopsy, underwent an identical 3T breast MRI protocol of the breast on two consecutive days (>24 h). Mean ADC of target lesions was assessed (two independent readers) in four separate sessions. Reproducibility, repeatability, and diagnostic accuracy between examinations (E1, E2), readers (R1, R2), and measurements (M1, M2) were assessed with intraclass correlation coefficients (ICCs), coefficients of variation (CVs), Bland–Altman plots, and receiver operating characteristic (ROC) analysis with calculation of the area under the ROC curve (AUC). The standard of reference was either histopathology (n = 38) or imaging follow‐up of up to 24 months (n = 2). Eighty breast MRI examinations (median E1–E2, 2 ± 1.7 days, 95% confidence interval (CI) 1–2 days, range 1–11 days) in 40 patients (mean age 56, standard deviation (SD) ±14) were evaluated. In 55 target lesions (mean size 25.2 ± 20.8 (SD) mm, range 6–106 mm), mean ADC values were significantly (P < 0.0001) higher in benign (1.38, 95% CI 1.27–1.49 × 10^?3 mm²/s) compared with malignant (0.86, 95% CI 0.81–0.91 × 10^?3 mm²/s) lesions. Reproducibility and repeatability showed high agreement for repeated examinations, readers, and measurements (all ICCs >0.9, CVs 3.2–8%), indicating little variation. Bland–Altman plots demonstrated no systematic differences, and diagnostic accuracy was not significantly different in the two repeated examinations (all ROC curves >0.91, P > 0.05). High reproducibility, repeatability, and diagnostic accuracy of DWI provide reliable characteristics for its use as a potential QIB, to further improve breast lesion detection, characterization, and treatment monitoring of breast lesions.     

Early detection of radiation therapy response in non‐Hodgkin's lymphoma xenografts by in vivo 1H magnetic resonance spectroscopy and imaging

The purpose of the study was to investigate the capability of ¹H MRS and MRI methods for detecting early response to radiation therapy in non‐Hodgkin's lymphoma (NHL). Studies were performed on the WSU‐DLCL2 xenograft model in nude mice of human diffuse large B‐cell lymphoma, the most common form of NHL. Radiation treatment was applied as a single 15 Gy dose to the tumor. Tumor lactate, lipids, total choline, T₂ and apparent diffusion coefficients (ADC) were measured before treatment and at 24 h and 72 h after radiation. A Hadamard‐encoded slice‐selective multiple quantum coherence spectroscopy sequence was used for detecting lactate (Lac) while a stimulated echo acquisition mode sequence was used for detection of total choline (tCho) and lipids. T₂‐ and diffusion‐weighted imaging sequences were used for measuring T₂ and ADC. Within 24 h after radiation, significant changes were observed in the normalized integrated resonance intensities of Lac and the methylenes of lipids. Lac/H₂O decreased by 38 ± 15% (p = 0.03), and lipid (1.3 ppm, CH₂)/H₂O increased by 57 ± 14% (p = 0.01). At 72 h after radiation, tCho/H₂O decreased by 45 ± 14% (p = 0.01), and lipid (2.8 ppm, polyunsaturated fatty acid)/H₂O increased by 970 ± 36% (p = 0.001). ADC increased by 14 ± 2% (p = 0.003), and T₂ did not change significantly. Tumor growth delay and regression were observed thereafter. This study enabled comparison of the relative sensitivities of various ¹H MRS and MRI indices to radiation and suggests that ¹H MRS/MRI measurements detect early responses to radiation that precede tumor volume changes. Copyright © 2010 John Wiley & Sons, Ltd.