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The aim of this study is to compare a qualitative and a quantitative assessment of brain diffusion-weighted imaging (DWI) in predicting outcome of comatose patients after cardiac arrest (CA). Two observers used a scoring template to analyze the DWI of 75 patients. A total of 13 regions were scored from 0 to 3 (0 = normal, 1 = probably normal, 2 = probably abnormal, 3 = definitely abnormal). The total cerebral cortex (TCC), the total deep grey nuclei (TDGN), the total brain stem, the total cerebellum, and the total brain score were calculated. Intra- and inter-observer variability were tested. The mean whole brain apparent diffusion coefficient (ADC) values and percentage of voxels below a specific ADC value cut-off were calculated. The data were correlated with clinical outcome (cerebral performance category score after 180 days, dichotomized in a score 1–2 with favorable outcome and score 3–5 with unfavorable outcome) using ROC analysis. Intra-observer variability was excellent for the TCC score (ICC 0.95 and 0.86) and the TDGN score (ICC 0.89 and 0.75). Inter-observer variability was good to excellent for total cerebral cortex score and total deep grey nuclei score in both the first (ICC 0.78 and 0.69) and third (ICC 0.86 and 0.83) image assessment. TCC and TDGN score show the best correlation with clinical outcome (highest AUC values 0.87 and 0.87). Quantitative parameters did not show good correlation with clinical outcome (AUC values 0.57 and 0.60). A qualitative assessment of brain DWI using a scoring template provides useful data regarding patient outcome while quantitative data appeared less reliable.

Background: Metastatic renal cell carcinoma (mRCC) patients with bone metastases (BM) are at high risk for skeletal related events and have a poorer outcome when treated with vascular endothelial g...

To facilitate the development of new brain metastasis (BM) treatment, an easy-to-use and clinically relevant animal model with imaging platform is needed. Rhabdomyosarcoma BM was induced in WAG/Rij rats. Post-implantation surveillance and characterizations were systematically performed with multiparametric MRI including 3D T1 and T2 weighted imaging, diffusion-weighted imaging (DWI), T1 and T2 mapping, and perfusion-weighted imaging (PWI), which were validated by postmortem digital radiography (DR), µCT angiography and histopathology. The translational potential was exemplified by the application of a vascular disrupting agent (VDA). BM was successfully induced in most rats of both genders (18/20). Multiparametric MRI revealed significantly higher T2 value, pre-contrast-enhanced (preCE) T1 value, DWI-derived apparent diffusion coefficient (ADC) and CE ratio, but a lower post-contrast-enhanced (postCE) T1 value in BM lesions than in adjacent brain (p 0.01). PWI showed the dynamic and higher contrast agent uptake in the BM compared with the adjacent brain. DR, µCT and histopathology characterized the BM as hypervascular tumors. After VDA treatment, the BM showed drug-related perfusion changes and partial necrosis as evidenced by anatomical, functional MRI parameters and postmortem findings. The present BM model and imaging modalities represent a feasible and translational platform for developing BM-targeting therapeutics.

To better inform the next clinical trials of vascular disrupting agent combretastatin-A4-phosphate (CA4P) in patients with hepatic malignancies, this preclinical study aimed at evaluating CA4P therapeutic efficacy in rats with primary hepatocellular carcinomas (HCCs) of a full spectrum of differentiation and vascularity by magnetic resonance imaging (MRI), microangiography and histopathology. Ninety-six HCCs were raised in 25 rats by diethylnitrosamine gavage. Tumor growth was monitored by T2-/T1-weighted-MRI (T2WI, T1WI) using a 3.0 T scanner. Early vascular response and later intratumoral necrosis were detected by dynamic-contrast-enhanced (DCE) MRI and diffusion-weighted-imaging (DWI) before, 1 and 12 hr after CA4P iv-administration. In vivo MRI-findings were validated by postmortem-techniques. Multi-parametric MRI revealed rapid CA4P-induced tumor vascular shutdown within 1 hr, followed by variable intratumoral necrosis at 12 hr. Tumor volumes decreased by 10% at 1 hr (p

Age-related brain atrophy is a common finding, but neurodegenerative diseases such as Alzheimer's disease are associated with accelerated atrophy of the medial temporal lobe. In current practice for brain atrophy evaluation, several rating scales are being used such as the medial temporal atrophy (MTA), global cortical atrophy-frontal subscale (GCA-F) and posterior atrophy (PA) scales. Practical cut-offs to differentiate between normal and advanced brain atrophy are needed, because of their possible usefulness as a biomarker. A retrospective study was performed over a 1-year period resulting in a total of 79 subjects [27 patients with Alzheimer's disease (AD), 27 patients with minimal cognitive impairment (MCI) and 25 control subjects]. The MTA, GCA-F and PA scales were applied blinded and independent by two raters. Possible age- and disease-related cut-offs were computed. The MTA scale showed significantly better diagnostic performances and inter-rater agreement than the PA and GCA-F scales. We could not confirm the suggested MTA cut-off for each decade. However, an MTA score of >1 and >1.75 was considered pathological, respectively, in the population under and over 70 years. MTA can be of use in making distinction between age-related atrophy and abnormal increase of atrophy. Systematic assessment of regional brain atrophy through the use of MTA in MRI images could be a useful biomarker in aiding the early diagnosis of Alzheimer's disease.

Despite excellent per-lesion performance for peritoneal staging, the additional clinical value of diffusion-weighted magnetic resonance imaging (DWI/MRI) compared to computed tomography (CT) remains to be established in ovarian cancer. Our purpose was to evaluate whole body (WB)-DWI/MRI for diagnosis, staging and operability assessment of patients suspected for ovarian cancer compared to CT. One hundred and sixty-one patients suspected for ovarian carcinoma underwent 3 T WB-DWI/MRI and contrast-enhanced CT. WB-DWI/MRI and CT were compared for confirmation of the malignant nature and primary origin of the ovarian mass, Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) staging and prediction of incomplete resection using institutional operability criteria. Interobserver agreement between two readers was determined for WB-DWI/MRI and CT. WB-DWI/MRI showed a significantly higher accuracy than CT (93 versus 82%, p = 0.001) to confirm the malignant nature of the ovarian mass and correctly identified 26 of 32 (81%) cancers of non-ovarian origin compared to 10/32 (31%) for CT (p < 0.001). WB-DWI/MRI assigned more ovarian carcinoma patients to the correct FIGO stage (82/94, 87%) compared with CT (33/94, 35%). For prediction of incomplete resection, WB-DWI/MRI showed significantly higher sensitivity (94 versus 66%), specificity (97.7 versus 77.3%) and accuracy (95.7 versus 71.3%) compared to CT (p < 0.001). Interobserver agreement was almost perfect (κ = 0.90) for WB-DWI/MRI and moderate (κ = 0.52) for CT for prediction of incomplete resection. WB-DWI/MRI was superior to CT for primary tumour characterisation, staging and prediction of incomplete resection in patients suspected for ovarian cancer

Introduction In head and neck squamous cell carcinoma (HNSCC) the ability to anticipate an individual patient's outcome is very valuable. With this study we wanted to assess the prognostic value of pretreatment apparent diffusion coefficient (ADC) in a large patient population and integrate it into a multivariable prognostic model. Methods From 2004 to 2010 175 patients with pathology proven HNSCC were included in this study. All patients underwent a pretreatment MRI with diffusion weighted imaging (DWI) using six b -values. For each tumor, three ADC values were calculated using different b -value combinations: ADC low ( b 0–50–100s/mm 2 ), ADC high ( b 500–750–1000s/mm 2 ) and ADC avg (all b -values). The clinical and radiological variables included: tumor and nodal volume, tumor location and age. Disease recurrence was analyzed using competing risk regression. A prognostic model for disease recurrence was developed, and internal validation was performed using bootstrapping and by dividing patients in three equal sized groups based on prognosis. Results One hundred and sixty-one patients were eligible for analysis. Median follow-up was 50months (range 4–86). A total of 67 patients experienced disease recurrence during follow-up (42%). ADC high was a prognostic factor for disease recurrence (adjusted hazard ratio: 1.14 per 10 –4 mm 2 /s, 95% CI 1.04–1.25). Harrell's c-index of the multivariable prognostic model was 0.62 (95% CI 0.56–0.70) after internal validation. The validated 3-year disease recurrence rates for the groups with worst, intermediate, and best prognosis were 56%, 33% and 31% respectively. Conclusion Pretreatment ADC value derived from high b -values is an independent prognostic factor in HNSCC and increases the performance of a multivariable prognostic model in addition to known clinical and radiological variables. Integration of other biomarkers and external validation is necessary to ensure its clinical applicability.

In head and neck cancer, diffusion weighted MRI (DWI) can predict response early during treatment. Treatment-induced changes and DWI-specific artifacts hinder an accurate registration between apparent diffusion coefficient (ADC) maps. The aim of the study was to develop a registration tool which calculates and visualizes regional changes in ADC.Twenty patients with stage IV HNC treated with primary radiotherapy received an MRI including DWI before and early during treatment. Markers were manually placed at anatomical landmarks on the different modalities at both time points. A registration method, consisting of a fully automatic rigid and nonrigid registration and two semi-automatic thin-plate spline (TPS) warps was developed and applied to the image sets. After each registration step the mean registration errors were calculated and ΔADC was compared between good and poor responders.Adding the TPS warps significantly reduced the registration error (in mm, 6.3 ± 6.2 vs 3.2 ± 3.3 mm, p0.001). After the marker based registration the median ΔADC in poor responders was significantly lower than in good responders (7% vs. 21%; p0.001).This registration method allowed for a significant reduction of the mean registration error. Furthermore the voxel-wise calculation of the ΔADC early during radiotherapy allowed for a visualization of the regional differences of ΔADC within the tumor.

We assessed the diagnostic accuracy of diffusion kurtosis imaging (DKI), dynamic susceptibility-weighted contrast-enhanced (DSC) MRI, and short echo time chemical shift imaging (CSI) for grading gliomas. In this prospective study, 35 patients with cerebral gliomas underwent DKI, DSC, and CSI on a 3 T MR scanner. Diffusion parameters were mean diffusivity (MD), fractional anisotropy, and mean kurtosis (MK). Perfusion parameters were mean relative regional cerebral blood volume (rrCBV), mean relative regional cerebral blood flow (rrCBF), mean transit time, and relative decrease ratio (rDR). The diffusion and perfusion parameters along with 12 CSI metabolite ratios were compared among 22 high-grade gliomas and 14 low-grade gliomas (Mann-Whitney U-test, P < .05). Classification accuracy was determined with a linear discriminant analysis for each MR modality independently. Furthermore, the performance of a multimodal analysis is reported, using a decision-tree rule combining the statistically significant DKI, DSC-MRI, and CSI parameters with the lowest P-value. The proposed classifiers were validated on a set of subsequently acquired data from 19 clinical patients. Statistically significant differences among tumor grades were shown for MK, MD, mean rrCBV, mean rrCBF, rDR, lipids over total choline, lipids over creatine, sum of myo-inositol, and sum of creatine. DSC-MRI proved to be the modality with the best performance when comparing modalities individually, while the multimodal decision tree proved to be most accurate in predicting tumor grade, with a performance of 86%. Combining information from DKI, DSC-MRI, and CSI increases diagnostic accuracy to differentiate low- from high-grade gliomas, possibly providing diagnosis for the individual patient.

To examine the feasibility and results of calculating the volume of lumbar vertebral bodies in normal patients and patients with suspected hypoplasia of L5. Lumbar multi-detector CT was performed in 38 patients with bilateral spondylolysis and hypoplasia of L5 and in 38 normal patients. Lumbar vertebral body volume of L3, L4 and L5 was measured by CT volumetry with a semi-automated program, created with MeVisLab. In the control group, the average vertebral body volume (in cubic centimeters) of L3 was 35.93 (±7.33), 36.34 (±7.13) for L4 and 34.63 (±6.88) for L5. In patients with suspected hypoplasia L5 the average body volume (in cubic centimeters) of L3 was 36.85 (±7.37), 36.90 (±6.99) for L4 and 33.14 (±6.57) for L5. The difference in mean vertebral body volume for L3, L4 and L5 between both groups was statistically not significant. However, there was a statistically significant difference of the ratio L5/L4 (P

Purpose To evaluate diffusion-weighted imaging (DWI) for assessment of treatment response in head and neck squamous cell carcinoma (HNSCC) three weeks after the end of chemoradiotherapy (CRT). Methods and Materials Twenty-nine patients with HNSCC underwent magnetic resonance imaging (MRI) prior to and 3 weeks after CRT, including T 2 -weighted and pre- and postcontrast T 1 -weighted sequences and an echo-planar DWI sequence with six b values (0 to 1,000 s/mm 2 ), from which the apparent diffusion coefficient (ADC) was calculated. ADC changes 3 weeks posttreatment compared to baseline (∆ADC) between responding and nonresponding primary lesions and adenopathies were correlated with 2 years locoregional control and compared with a Mann-Whitney test. In a blinded manner, the ∆ADC was compared to conventional MRI 3 weeks post-CRT and the routinely implemented CT, on average 3 months post-CRT, which used size-related and morphological criteria. Positive and negative predictive values (PPV and NPV, respectively) were compared between the ∆ADC and anatomical imaging. Results The ∆ADC of lesions with later tumor recurrence was significantly lower than lesions with complete remission for both primary lesions (−2.3% ± 0.3% vs. 80% ± 41%; p p = 0.003). The ∆ADC showed a PPV of 89% and an NPV of 100% for primary lesions and a PPV of 70% and an NPV of 96% for adenopathies per neck side. DWI improved PPV and NPV compared to anatomical imaging. Conclusion DWI with the ∆ADC 3 weeks after concluding CRT for HNSCC allows for early assessment of treatment response.

Purpose To evaluate the use of semi-quantitative dynamic contrast-enhanced MRI (DCE-MRI) parameters for the detection of prostatic carcinoma in correlation to whole-mount histopathology. Materials and methods Fifty-three patients with biopsy-proven prostate cancer were examined by DCE-MRI at 1.5-T. Cancerous and benign prostatic tissue regions of interest were delineated based on the histopathology of whole-mount sections and several semi-quantitative parameters were calculated: time to peak (TTP), maximal contrast enhancement (Cpeak), speed of contrast uptake (Wash-in) and clearance rate of the contrast agent (Wash-out). The area under the ROC curve was determined for each parameter. Results Within individual patients, a consistently higher Cpeak and faster Wash-in were present in cancerous compared to benign prostatic tissue. Both the TTP and the Wash-out occurred more rapidly in tumour tissue than in normal prostatic tissue. Despite a considerable inter-patient overlap of parameter values between tumour and normal prostatic tissue, area under the ROC curve analysis demonstrated that the Wash-in was a good discriminator for cancer and benign tissue (AUC 0.82). Combination of the Wash-in and the Wash-out proved to be even more accurate (AUC 0.87) to discriminate between cancerous and benign prostatic regions. Conclusion The Wash-in is a useful parameter for prostate cancer detection by DCE-MRI.

To compare a commercial contrast agent (CA) Dotarem and a necrosis-avid CA (NACA) for their ability to evaluate the therapeutic necrosis with a vascular disrupting agent (VDA) on magnetic resonance imaging in rodent liver tumors to determine which could better correlate with the histopathologic outcome.: After the VDA treatment, 16 rats with 32 liver rhabdomyosarcomas were randomized into Dotarem and NACA groups (n = 8 per group) for both interindividual and intraindividual comparisons. T2-weighted imaging, T1-weighted imaging (T1WI), contrast-enhanced T1-weighted imaging (CE-T1WI), and diffusion-weighted imaging were performed at baseline, after VDA treatment and CA injections. The enhancing efficacy of CAs at immediate and delayed enhancement on CE-T1WI in viable tumor and necrosis was compared. Tumor necrosis ratios calculated from NACA and Dotarem were compared and correlated with gold-standard histopathology.: On the immediate CE-T1WI, viable tumor was enhanced by either CA. On the delayed CE-T1WI at 30 minutes, both CAs failed to demarcate viable tumor from necrosis. At 24 hours post-NACA, the necrosis was clearly distinguished from viable tumor and thus derived necrosis ratio matched that from histopathology (P = 0.99); necrosis ratio from Dotarem was significantly lower than that from NACA and histopathology (P0.05, both), with a higher correlation of NACA than that of Dotarem with histopathology (r = 0.99 vs. r = 0.82).: NACA better evaluated VDA-induced tumor necrosis than nonspecific CA on T1WI in tumor models of rat liver. NACA showed a closer correlation with histopathology than nonspecific CA for the delineation of true necrosis. Delayed enhancement on T1WI with nonspecific CA is not suitable for the assessment of VDA-induced tumor necrosis.

BACKGROUND Correct staging and treatment initiation in malignant lymphoma depends on accurate lymph node characterization. However, nodal assessment based on conventional and diffusion-weighted (DWI) MRI remains challenging, particularly in smaller nodes. PURPOSE To evaluate first-order apparent diffusion coefficient (ADC) texture parameters compared to mean ADC for lymph node characterization in non-Hodgkin lymphoma (NHL) using whole-body DWI (WB-DWI). STUDY TYPE Retrospective. POPULATION Twenty-eight patients with NHL. FIELD STRENGTH/SEQUENCE 3T whole-body DWI using two b-values (0-1000 s/mm2 ). ASSESSMENT Regions of interest were drawn on the three most hyperintense lymph nodes on b1000-images, irrespective of size, in all nodal body regions. Diagnostic performance of mean ADC (ADCmean ) was compared with first-order ADC texture parameters: standard deviation (ADCstdev ), kurtosis (ADCkurt ), and skewness (ADCskew ). Additional subanalyses focused on the accuracy of ADCmean and ADC texture parameters in different lymph node volumes and nodal regions. STATISTICAL TESTS Benign and malignant nodes were compared using Mann-Whitney U-tests with 18-Fluoro-deoxyglucose positron emission tomography computed tomography and bone marrow biopsy as reference standard. Receiver operating characteristic analyses were performed to determine cutoff values and calculate sensitivity, specificity, accuracy, and positive and negative predictive value (PPV, NPV). RESULTS ADCmean (P = 0.008), ADCskew and ADCkurt differed significantly between benign and malignant nodes (P

With the association of concurrent chemotherapy, the widespread implementation of altered fractionation schedules and the use of more conformal radiotherapy techniques, the locoregional management of patients with squamous cell carcinoma of the head and neck region (HNSCC) has greatly improved over the last decades. However, associated toxicity has reached the limits of acceptability. If we want to further improve the therapeutic index of HNSCC we will need to target the tumor more accurately while sparing the surrounding organs at risk as much as possible. Therefore, accurate detection and delineation of tumor areas is essential, and diffusion-weighted MRI (DW-MRI) might help us in this task. DW-MRI can characterize tissues and generate image contrast based on differences in water mobility. Thus, while conventional imaging techniques such as computed tomography and MRI depict anatomical structures, functional imaging techniques such as DW-MRI provide us with a deeper insight in the tumor's underlying biological activity and microstructural characteristics. In this article, we aim to bundle the current experience on DW-MRI in HNSCC and elaborate on its potential value and drawbacks at different time points before, during and after radiotherapy.

In the head and neck, squamous cell carcinoma is one of the most common tumour types. Currently, the primary imaging modalities for initial locoregional staging are computed tomography and-to a lesser extent-magnetic resonance imaging, whilst [(18)F]fluorodeoxyglucose (FDG) positron emission tomography has additional value in the detection of subcentimetric metastatic lymph nodes and of tumour recurrence after chemoradiotherapy (CRT). However, dependency on the morphological and size-related criteria of anatomical imaging and the limited spatial resolution and FDG avidity of inflammation in metabolic imaging may reduce diagnostic accuracy in the head and neck. Diffusion-weighted magnetic resonance imaging (DWI) is a noninvasive imaging technique that measures the differences in water mobility in different tissue microstructures. Water mobility is likely influenced by cell size, density, and cellular membrane integrity and is quantified by means of the apparent diffusion coefficient. As such, the technique is able to differentiate tumoural tissue from normal tissue, inflammatory tissue and necrosis. In this article, we examine the use of DWI in head and neck cancer, focussing on technique optimization and image interpretation. Afterwards, the value of DWI will be outlined for clinical questions regarding nodal staging, lesion characterization, differentiation of post-CRT tumour recurrence from necrosis and inflammation, and predictive imaging towards treatment outcome. The possible consequences of adding DWI towards therapeutic management are outlined.

Purpose . To investigate the use of FDG-PET/CT before, during and after chemoradiotherapy (CRT) and diffusionweighted magnetic resonance imaging (DW-MRI) before CRT for the prediction of pathological response (pCR) in rectal cancer patients. Material and methods . Twenty-two rectal cancer patients treated with long course CRT were included. An FDG-PET/CT was performed prior to the start of CRT, after 10 to 12 fractions of CRT and fi ve weeks after the end of CRT. The tumor was delineated using a gradient based delineation method and the maximal standardized uptake values (SUV max ) were calculated. A DW-MRI was performed before start of CRT. Mean apparent diffusion coeffi cients (ADC) were determined. The Δ SUV max during and after CRT and the initial ADC values were correlated to the histopathological fi ndings after total mesorectal excision (TME). Results. Δ SUV max during and after CRT signifi cantly correlated with the pathological response to treatment (during CRT: Δ SUV max 59% 12% for pCR vs. 25% 27% if no pCR, p 0.0036; post-CRT: 90% 11 for pCR vs. 63% 22 if no pCR p 0.013). ROC curve analysis revealed an optimal threshold for Δ SUV max of 40% during CRT and 76% after CRT. The initial ADC value was also signifi cantly correlated with pCR (0.94 0.12 10 3 mm ≤ /s for pCR vs. 1.2 0.24 10 3 mm ≤ /s, p 0.002) and ROC curve analysis revealed an optimal threshold of 1.06 10 3 mm ≤ /s. Combining the provided Δ SUV max thresholds during and after CRT increased specifi city of the prediction (sensitivity 100% and specifi city 94%). The combination of the thresholds for the initial ADC value and the Δ SUV max during CRT increased specifi city of the prediction to a similar level (sensitivity of 100% and specifi city of 94%). Conclusions . The combination of the different time points and the different imaging modalities increased the specifi city of the response assessment both during and after CRT.

Purpose To evaluate the use of diffusion-weighted magnetic resonance imaging (DW-MRI) for nodal staging and its impact on radiotherapy (RT) planning. Methods and Materials Twenty-two patients with locally advanced head and neck squamous cell carcinoma underwent contrast-enhanced computed tomography (CT), as well as MRI (with routine and DW sequences) prior to neck dissection. After topographic correlation, lymph nodes were evaluated microscopically with prekeratin immunostaining. Pathology results were correlated with imaging findings and an RT planning study was performed for these surgically treated patients. One set of target volumes was based on conventional imaging only, and another set was based on the corresponding DW-MRI images. A third reference set was contoured based solely on pathology results. Results A sensitivity of 89% and a specificity of 97% per lymph node were found for DW-MRI. Nodal staging agreement between imaging and pathology was significantly stronger for DW-MRI (κ = 0.97; 95% confidence interval [CI], 0.84–1.00) than for conventional imaging (κ = 0.56; 95% CI, 0.16–0.96; p = 0.019, by McNemar's test). For both imaging modalities, the absolute differences between RT volumes and those obtained by pathology were calculated. Using an exact paired Wilcoxon test, the observed difference was significantly larger for conventional imaging than for DW-MRI for nodal gross tumor volume ( p = 0.0013), as well as for nodal clinical target volume ( p = 0.0415) delineation. Conclusions These results suggest that DW-MRI is superior to conventional imaging for preradiotherapy nodal staging of head and neck squamous cell carcinoma, and provides a potential impact on organsparing and tumor control.

OBJECTIVES: To document tumoricidal events after intravenous administration of a vascular targeting agent combretastatin A-4-phosphate (CA4P) in rodent liver tumors by using multiparametric magnetic resonance imaging (MRI) in correlation with microangiography and histopathology. MATERIALS AND METHODS: Thirty rhabdomyosarcomas of 8 to 14 mm in diameter were obtained 16 days after implantation in liver lobes of 15 rats. Using a 1.5T magnet and a 4-channel wrist coil, T2-weighted imaging (T2WI), pre- and postcontrast T1-weighted imaging (T1WI), diffusion-weighted imaging (DWI), and dynamic susceptibility imaging (DSI) with relative blood volume (rBV) and flow (rBF) maps were acquired at baseline, 1 hour, 6 hours, and 48 hours after iv injection of CA4P at 10 mg/kg and vehicle in 9 treated and 6 control rats, respectively. In vivo data including signal intensity (SI), tumor volume, apparent diffusion coefficient (ADC), rBV, and rBF were correlated with ex vivo microangiographic and histopathologic findings. RESULTS: CA4P-treated tumors (n = 18) grew slower than those (n = 12) of controls (P < 0.05), with vascular shutdown evident on CE-T1WI at 1 hour but more prominent at 6 hours. However, enhanced rim occurred in the periphery 48 hours after treatment, indicating neovascularization. ADC map enabled distinction between necrotic and viable tumors. DSI-derived tumoral rBV and rBF decreased significantly at 1 hour through 6 hours and partly recovered at 48 hours. SI-time curve reflected diverse therapeutic responses between tumor and liver. MRI findings were verified by ex vivo techniques. CONCLUSIONS: Clinical MRI allowed monitoring of CA4P-related vascular shutdown, necrosis, and neovascularization of liver tumors in rats. Single dose of CA4P seemed insufficient for tumor eradication because of evident peripheral residue and recurrence. ispartof: Investigative Radiology vol:44 issue:1 pages:44-53 ispartof: location:United States status: published

The advent of new antitumoral agents targeting tumoral vascularity require a change of diagnostic strategy. Imaging modalities should aim at detecting treatment-induced intratumoral changes as treatment success not necessarily leads to a substantial loss of tumor volume. The tumoral vasculature and cellular microstructure offer attractive diagnostic targets for functional magnetic resonance imaging (MRI)-techniques. Dynamic contrast-enhanced (DCE)-MRI demonstrates tissue perfusion and permeability and can be used as a pharmacodynamic indicator for the efficacy of antivascular treatment. Diffusion-weighted (DW)-MRI allows for tissue differentiation based on changes in tissular water mobility, acting as a surrogate marker for microstructural density. By its ability to differentiate intact tumoral tissue from necrosis, DW-MRI can be used for early assessment of tumor response to systemic treatment. The aim of this paper is to discuss the background, basic principles and potential applications of perfusion- and diffusion-MRI for follow-up of treatment with angiogenesis inhibitors.

Rationale and Objectives We sought to assess changes in liver perfusion parameters induced by transjugular intrahepatic portosystemic shunt (TIPS) creation in cirrhotic patients with refractory ascites using dynamic MR perfusion measurements. Materials and Methods MR perfusion measurements were performed before and after TIPS creation in 15 cirrhotic patients all with refractory ascites. Measurements were performed over a time period of 120 seconds providing 60 images for each examination and calculations were done in both liver and splenic parenchyma. Different perfusion parameters were assessed: time to peak (TTP), time to inflow deceleration (TID), maximal or peak perfusion (C-peak) and the wash-in rate. Results TIPS procedures were successful in all 15 patients but were complicated by hepatic encephalopathy in 3 patients (20%), and in another 4 patients (26%), persistent refractory ascites was still noted during follow-up. Overall, liver TID values decreased significantly ( P = .001) after TIPS creation; liver wash-in values increased significantly ( P = .04) after TIPS. TTP values did not decrease significantly ( P = .16) and liver C-peak values did not change equally ( P = .99). Conclusion In cirrhotic patients with refractory ascites, TIPS induced a faster, but not an increased, contrast enhancement in the liver.

Although fetal kidneys have only 10% of their postnatal blood flow, fetal renal development is essential for normal postnatal function. In addition, to our knowledge it is unknown whether human fetal kidney development follows a linear or exponential evolution. We created normative magnetic resonance imaging curves for the kidney prenatal growth pattern in relation to gestational age.A total of 142 human fetuses at between 20 and 36 weeks of gestation underwent prenatal magnetic resonance imaging for nonurological pathology (pulmonary, cerebral or maternal abnormalities). Twins, urinary tract abnormalities, oligohydramnios or anhydramnios were excluded. T2-weighted images (single shot turbo spin-echo) were used to measure kidney variables. Bipolar and anteroposterior diameters of the 2 kidneys were measured and correlated with gestational age using linear regression analysis.A linear relationship of the bipolar and anteroposterior diameters was found according to gestational age in weeks (p0.0001). No substantial differences between growth of the left and right fetal kidneys was identified. Bipolar length of the human fetal kidney increases at an average rate of 1.24 mm per week of gestation, while anteroposterior diameter increases at 0.57 mm per week of gestation between weeks 20 and 36. This indicates that bipolar diameter increases twice as rapidly as anteroposterior diameter. Regression analysis curves showed a good fit to the measured data points (anteroposterior and bipolar measurements R2 = 0.36 and 0.58, respectively). The CIs of function variables were small, enabling their use as normative curves.This prenatal magnetic resonance imaging study demonstrates linear growth of the bipolar and anteroposterior diameters of human fetal kidneys in relation to gestational age. In addition, it is clear that bipolar diameter grows twice as rapidly as anteroposterior diameter and there is less variability for bipolar diameter. These normative curves may allow us to detect abnormal fetal evolution.

To characterize pancreatic perfusion in volunteers and patients with chronic pancreatitis (CP) by dynamic contrast-enhanced (DCE) MRI.Pancreatic enhancement after bolus injection of Gd-DTPA with a three-dimensional ultrafast partial-Fourier radiofrequency (RF) spoiled gradient-echo (GE) acquisition was examined prospectively. An acquisition volume of the pancreatic parenchyma was obtained every 4.2 seconds during a single breath-hold in 31 volunteers and 19 patients with CP. We calculated the wash-in rate and a newly defined parameter, the "time-to-inflow deceleration" (TID). A statistical analysis of the differences between both groups was performed with the use of Student's t-test.Significant differences in the TID and wash-in rate were found for the head and body of the pancreas: the TID was 22.4 sec +/- 4.4 sec and 23.5 sec +/- 6.1 sec in the pancreatic head and body of the healthy volunteers, and 29.8 sec +/- 8.6 sec and 29.4 sec +/- 3.8 sec in patients with CP. The wash-in rate was 96 +/- 37 sec(-1) and 101 +/- 27 sec(-1) in controls, and 62 +/- 17 sec(-1) and 75 +/- 27 sec(-1) in CP.CP can be identified by semiquantitative changes on DCE-MRI. Whether DCE-MRI of the pancreas can be used to detect early CP remains to be validated.

This work proposes a new method of building 3D breast mass models with different morphological shapes and describes the validation of the realism of their appearance after simulation into 2D digital mammograms and breast tomosynthesis images.Twenty-five contrast enhanced MRI breast lesions were collected and each mass was manually segmented in the three orthogonal views: sagittal, coronal, and transversal. The segmented models were combined, resampled to have isotropic voxel sizes, triangularly meshed, and scaled to different sizes. These masses were referred to as nonspiculated masses and were then used as nuclei onto which spicules were grown with an iterative branching algorithm forming a total of 30 spiculated masses. These 55 mass models were projected into 2D projection images to obtain mammograms after image processing and into tomographic sequences of projection images, which were then reconstructed to form 3D tomosynthesis datasets. The realism of the appearance of these mass models was assessed by five radiologists via receiver operating characteristic (ROC) analysis when compared to 54 real masses. All lesions were also given a breast imaging reporting and data system (BIRADS) score. The data sets of 2D mammography and tomosynthesis were read separately. The Kendall's coefficient of concordance was used for the interrater observer agreement assessment for the BIRADS scores per modality. Further paired analysis, using the Wilcoxon signed rank test, of the BIRADS assessment between 2D and tomosynthesis was separately performed for the real masses and for the simulated masses.The area under the ROC curves, averaged over all observers, was 0.54 (95% confidence interval [0.50, 0.66]) for the 2D study, and 0.67 (95% confidence interval [0.55, 0.79]) for the tomosynthesis study. According to the BIRADS scores, the nonspiculated and the spiculated masses varied in their degrees of malignancy from normal (BIRADS 1) to highly suggestive for malignancy (BIRADS 5) indicating the required variety of shapes and margins of these models. The assessment of the BIRADS scores for all observers indicated good agreement based on Kendall's coefficient for both the 2D and the tomosynthesis evaluations. The paired analysis of the BIRADS scores between 2D and tomosynthesis for each observer revealed consistent behavior for the real and simulated masses.A database of 3D mass models, with variety of shapes and margins, was validated for the realism of their appearance for 2D digital mammography and for breast tomosynthesis. This database is suitable for use in future observer performance studies whether in virtual clinical trials or in patient images with simulated lesions.

A key problem in solid tumor therapy is tumor regrowth from a residual viable rim after treatment with a vascular disrupting agent (VDA). As a potential solution, we studied a combined treatment of a VDA and antiangiogenic. This study was approved by the institutional ethical committee for the use and care of laboratory animals. Rats with implanted liver tumors were randomized into four treatment groups: 1) Zd6126 (Zd); 2) Thalidomide (Tha); 3) Zd in combination with Tha (ZdTha); and 4) controls. Multiparametric MRIs were performed and quantified before and after treatment. Circulating endothelial progenitor cells (EPCs) and plasma stromal cell-derived factor-1α (SDF-1α) were monitored. Tumor apoptosis, necrosis, and microvessels were verified by histopathology. A single use of Zd or Tha did not significantly delay tumor growth. The combined ZdTha showed enhanced antitumor efficacy due to synergistic effects; it induced a cumulative tumor apoptosis or necrosis, which resulted in significant delay in tumor growth and reduction in the viable tumor rim; it also reduced tumor vessel permeability; and it improved tumor hemodynamic indexes, most likely via a transient normalization of tumor vasculature induced by Tha. A stepwise linear regression analysis showed that the apparent diffusion coefficient was an independent predictor of tumor growth. We found no significant increases in Zd-induced circulating EPCs or plasma SDF-1α. ZdTha showed improved therapeutic efficacy in solid tumors compared to either agent alone. The therapeutic effects were successfully tracked in vivo with multiparametric MRI.

Purpose To determine the feasibility of in vivo diffusion-weighted imaging (DWI) to distinguish between normal liver, viable tumor and necrosis compared to postmortem DWI in a rat model with vascular-targeting treatment. Materials and Methods Fifteen rats with liver implantation of 30 rhabdomyosarcomas were treated with combretastatin A-4-phosphate (CA4P) at 10 mg/kg. Two days after treatment, T2-weighted imaging, precontrast T1-weighted imaging, postcontrast T1-weighted imaging, and DWI were performed in vivo and postmortem with a 1.5T scanner. Apparent diffusion coefficients (ADCs) calculated from DWIs with b values of 0, 50, and 100 seconds/mm2 (ADClow), 500, 750, and 1000 seconds/mm2 (ADChigh), 0, 500, and 1000 seconds/mm2 (ADC3b), and 0–1000 seconds/mm2 (ADC10b) for tumor, liver, therapeutic necrosis, and phantoms were compared and validated with ex vivo microangiographic and histopathologic findings. Results Except ADClow between tumor and necrosis, in vivo ADCs successfully differentiated liver, viable tumor, and necrosis (P < 0.05). Compared to in vivo outcomes, postmortem ADCs significantly dropped in tumor and liver (P < 0.05) except ADChigh of tumor, but not in necrosis and phantoms. Compared to ADClow, ADChigh was less affected by vital status. Conclusion Advantageous over postmortem DWI, in vivo DWI provides a noninvasive easy-performing tool for distinguishing between liver, viable tumor, and necrosis. ADClow and ADChigh better reflect tissue perfusion and water diffusion, respectively. J. Magn. Reson. Imaging 2009;29:621–628. © 2009 Wiley-Liss, Inc.

To prospectively determine if changes in intrarenal oxygenation during acute unilateral ureteral obstruction can be depicted with blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging.The study was approved by the local ethics committee, and written informed consent was obtained from all patients. BOLD MR imaging was performed in 10 male patients (mean age, 45 years +/- 17 [standard deviation]; range, 20-73 years) with a distal unilateral ureteral calculus and in 10 healthy age-matched male volunteers to estimate R2*, which is inversely related to tissue Po(2). R2* values were determined in the cortex and medulla of the obstructed and the contralateral nonobstructed kidneys. To reduce external effects on R2*, the R2* ratio between the medulla and cortex was also analyzed. Statistical analysis was performed with nonparametric rank tests. P.05 was considered to indicate a significant difference.All patients had significantly lower medullary and cortical R2* values in the obstructed kidney (median R2* in medulla, 10.9 sec(-1) [range, 9.1-14.3 sec(-1)]; median R2* in cortex, 10.4 sec(-1) [range, 9.7-11.3 sec(-1)]) than in the nonobstructed kidney (median R2* in medulla, 17.2 sec(-1) [range, 14.6-23.2 sec(-1)], P = .005; median R2* in cortex, 11.7 sec(-1) [range, 11.0-14.0 sec(-1)], P = .005); values in the obstructed kidneys were also significantly lower than values in the kidneys of healthy control subjects (median R2* in medulla, 16.1 sec(-1) [range, 13.9-18.1 sec(-1)], P.001; median R2* in cortex, 11.6 sec(-1) [range, 10.5-12.9 sec(-1)], P.001). R2* ratios in the obstructed kidneys (median, 1.06; range, 0.85-1.27) were significantly lower than those in the nonobstructed kidneys (median, 1.49; range, 1.26-1.71; P = .005) and those in the kidneys of healthy control subjects (median, 1.38; range, 1.23-1.47; P.001). In contrast, R2* ratios in the nonobstructed kidneys of patients were significantly higher than those in kidneys of healthy control subjects (P = .01).Increased oxygen content in the renal cortex and medulla occurs with acute unilateral ureteral obstruction, suggesting reduced function of the affected kidney.

Purpose: To prospectively determine normal ranges of total fetal lung volume (TFLV) based on fetal body volume (FBV) and to determine whether prediction of TFLV based on such ranges is independent of fetal biometric indexes. Materials and Methods: The study was approved by the Ethics Committee on Clinical Studies; informed consent was obtained. Magnetic resonance imaging volumetric measurement of fetal lung, liver, and body was performed in 200 fetuses without abnormalities affecting these structures. FBV was assessed with planimetric measurements by using T2-weighted half-Fourier rapid acquisition with relaxation enhancement at 16-40 weeks of gestation. TFLV was correlated to gestational age (GA), liver volume, and FBV. Observed-expected (O/E) ratio for TFLV was calculated by expressing the observed TFLV as a percentage of the expected mean TFLV for GA, liver volume, or FBV. Three groups of fetuses were defined on the basis of biometric percentiles for fetal weight obtained through ultrasonography: fetuses with weight at or below the 5th percentile, those with weight at or above the 95th percentile, and those with weight between these two percentiles (eutrophic). Median O/E ratios, based on GA and FBV, in fetuses with weight below the 5th percentile and in those with weight above the 95th percentile, were compared with median O/E ratio of eutrophic fetuses (Mann-Whitney U test). Results: TFLV correlated best with FBV, according to the following cubic fit: TFLV = [(2.0 (.) 10(-9)) (.) FBV3] - [(1.19 (.) 10(-5)) (.) FBV2] + (0.0508 (.) FBV) - 1.79 (r(2) = 0.85, P

CONTEXT: Comparative reviews of whole-body magnetic resonance imaging (WB-MRI) and positron emission tomography/computed tomography (CT; with different radiotracers) have shown that metastasis detection in advanced cancers is more accurate than with currently used CT and bone scans. However, the ability of WB-MRI and positron emission tomography/CT to assess therapeutic benefits has not been comprehensively evaluated. There is also considerable variability in the availability and quality of WB-MRI, which is an impediment to clinical development. Expert recommendations for standardising WB-MRI scans are needed, in order to assess its performance in advanced prostate cancer (APC) clinical trials. OBJECTIVE: To design recommendations that promote standardisation and diminish variations in the acquisition, interpretation, and reporting of WB-MRI scans for use in APC. EVIDENCE ACQUISITION: An international expert panel of oncologic imagers and oncologists with clinical and research interests in APC management assessed biomarker requirements for clinical care and clinical trials. Key requirements for a workable WB-MRI protocol, achievable quality standards, and interpretation criteria were identified and synthesised in a white paper. EVIDENCE SYNTHESIS: The METastasis Reporting and Data System for Prostate Cancer guidelines were formulated for use in all oncologic manifestations of APC. CONCLUSIONS: Uniformity in imaging data acquisition, quality, and interpretation of WB-MRI are essential for assessing the test performance of WB-MRI. The METastasis Reporting and Data System for Prostate Cancer standard requires validation in clinical trials of treatment approaches in APC. PATIENT SUMMARY: METastasis Reporting and Data System for Prostate Cancer represents the consensus recommendations on the performance, quality standards, and reporting of whole-body magnetic resonance imaging, for use in all oncologic manifestations of advanced prostate cancer. These new criteria require validation in clinical trials of established and new treatment approaches in advanced prostate cancer.