Assessment of Treatment Response by Total Tumor Volume and Global Apparent Diffusion Coefficient Using Diffusion-Weighted MRI in Patients with Metastatic Bone Disease: A Feasibility Study

We describe our semi-automatic segmentation of whole-body diffusion-weighted MRI (WBDWI) using a Markov random field (MRF) model to derive tumor total diffusion volume (tDV) and associated global apparent diffusion coefficient (gADC); and demonstrate the feasibility of using these indices for assessing tumor burden and response to treatment in patients with bone metastases.WBDWI was performed on eleven patients diagnosed with bone metastases from breast and prostate cancers before and after anti-cancer therapies. Semi-automatic segmentation incorporating a MRF model was performed in all patients below the C4 vertebra by an experienced radiologist with over eight years of clinical experience in body DWI. Changes in tDV and gADC distributions were compared with overall response determined by all imaging, tumor markers and clinical findings at serial follow up. The segmentation technique was possible in all patients although erroneous volumes of interest were generated in one patient because of poor fat suppression in the pelvis, requiring manual correction. Responding patients showed a larger increase in gADC (median change = +0.18, range = −0.07 to +0.78×10⁻³ mm²/s) after treatment compared to non-responding patients (median change = −0.02, range = −0.10 to +0.05×10⁻³ mm²/s, p = 0.05, Mann-Whitney test), whereas non-responding patients showed a significantly larger increase in tDV (median change = +26%, range = +3 to +284%) compared to responding patients (median change = −50%, range = −85 to +27%, p = 0.02, Mann-Whitney test). Semi-automatic segmentation of WBDWI is feasible for metastatic bone disease in this pilot cohort of 11 patients, and could be used to quantify tumor total diffusion volume and median global ADC for assessing response to treatment.     

A Potential Risk of Overestimating Apparent Diffusion Coefficient in Parotid Glands

Objectives

To investigate transient signal loss on diffusion weighted images (DWI) and overestimation of apparent diffusion coefficient (ADC) in parotid glands using single shot echoplanar DWI (EPDWI).

Materials and Methods

This study enrolled 6 healthy subjects and 7 patients receiving radiotherapy. All participants received dynamic EPDWI with a total of 8 repetitions. Imaging quality of DWI was evaluated. Probability of severe overestimation of ADC (soADC), defined by an ADC ratio more than 1.2, was calculated. Error on T2WI, DWI, and ADC was computed. Statistical analysis included paired Student t testing and Mann-Whitney U test. A P value less than 0.05 was considered statistically significant.

Results

Transient signal loss was visually detected on some excitations of DWI but not on T2WI or mean DWI. soADC occurred randomly among 8 excitations and 3 directions of diffusion encoding gradients. Probability of soADC was significantly higher in radiotherapy group (42.86%) than in healthy group (24.39%). The mean error percentage decreased as the number of excitations increased on all images, and, it was smallest on T2WI, followed by DWI and ADC in an increasing order.

Conclusions

Transient signal loss on DWI was successfully detected by dynamic EPDWI. The signal loss on DWI and overestimation of ADC could be partially remedied by increasing the number of excitations.     

Nuclear Overhauser Enhancement Imaging of Glioblastoma at 7 Tesla: Region Specific Correlation with Apparent Diffusion Coefficient and Histology

Objective

To explore the correlation between Nuclear Overhauser Enhancement (NOE)-mediated signals and tumor cellularity in glioblastoma utilizing the apparent diffusion coefficient (ADC) and cell density from histologic specimens. NOE is one type of chemical exchange saturation transfer (CEST) that originates from mobile macromolecules such as proteins and might be associated with tumor cellularity via altered protein synthesis in proliferating cells.

Patients and Methods

For 15 patients with newly diagnosed glioblastoma, NOE-mediated CEST-contrast was acquired at 7 Tesla (asymmetric magnetization transfer ratio (MTR_asym) at 3.3ppm, B1 = 0.7 μT). Contrast enhanced T1 (CE-T1), T2 and diffusion-weighted MRI (DWI) were acquired at 3 Tesla and coregistered. The T2 edema and the CE-T1 tumor were segmented. ADC and MTR_asym values within both regions of interest were correlated voxelwise yielding the correlation coefficient r_Spearman (r_Sp). In three patients who underwent stereotactic biopsy, cell density of 12 specimens per patient was correlated with corresponding MTR_asym and ADC values of the biopsy site.

Results

Eight of 15 patients showed a weak or moderate positive correlation of MTR_asym and ADC within the T2 edema (0.16≤r_Sp≤0.53, p<0.05). Seven correlations were statistically insignificant (p>0.05, n = 4) or yielded r_Sp≈0 (p<0.05, n = 3). No trend towards a correlation between MTR_asym and ADC was found in CE-T1 tumor (-0.31<r_Sp<0.28, p<0.05, n = 9; p>0.05, n = 6). The biopsy-analysis within CE-T1 tumor revealed a strong positive correlation between tumor cellularity and MTR_asym values in two of the three patients (r_Sp ^patient3 = 0.69 and r_Sp ^patient15 = 0.87, p<0.05), while the correlation of ADC and cellularity was heterogeneous (r_Sp ^patient3 = 0.545 (p = 0.067), r_Sp ^patient4 = -0.021 (p = 0.948), r_Sp ^patient15 = -0.755 (p = 0.005)).

Discussion

NOE-imaging is a new contrast promising insight into pathophysiologic processes in glioblastoma regarding cell density and protein content, setting itself apart from DWI. Future studies might be based on the assumption that NOE-mediated CEST visualizes cellularity more accurately than ADC, especially in the CE-T1 tumor region.     

Histogram Analysis Parameters Apparent Diffusion Coefficient for Distinguishing High and Low-Grade Meningiomas: A Multicenter Study

Low grade meningiomas have better prognosis than high grade meningiomas. The aim of this study was to measure apparent diffusion coefficient (ADC) histogram analysis parameters in different meningiomas in a large multicenter sample and to analyze the possibility of several parameters for predicting tumor grade and proliferation potential. Overall, 148 meningiomas from 7 institutions were evaluated in this retrospective study. Grade 1 lesions were diagnosed in 101 (68.2%) cases, grade 2 in 41 (27.7%) patients, and grade 3 in 6 (4.1%) patients. All tumors were investigated by MRI (1.5 T scanner) by using diffusion weighted imaging (b values of 0 and 1000 s/mm²). For every lesion, the following parameters were calculated: mean ADC, maximum ADC, minimum ADC, median ADC, mode ADC, ADC percentiles P10, P25, P75, P90, kurtosis, skewness, and entropy. The comparison of ADC values was performed by Mann–Whitney-U test. Correlation between different ADC parameters and KI 67 was calculated by Spearman's rank correlation coefficient. Grade 2/3 meningiomas showed statistically significant lower ADC histogram analysis parameters in comparison to grade 1 tumors, especially ADC median. A threshold value of 0.82 for ADC median to predict tumor grade was estimated (sensitivity?=?82.2%, specificity?=?63.8%, accuracy?=?76.4%, positive and negative predictive values were 83% and 62.5%, respectively).All ADC parameters except maximum ADC showed weak significant correlations with KI 67, especially ADC P25 (P?=??.340, P?=?.0001).     

Spatiotemporal Correlations between Blood-Brain Barrier Permeability and Apparent Diffusion Coefficient in a Rat Model of Ischemic Stroke

Variations in apparent diffusion coefficient of water (ADC) and blood-brain barrier (BBB) permeability after ischemia have been suggested, though the correlation between ADC alterations and BBB opening remains to be studied. We hypothesized that there are correlations between the alteration of ADC and BBB permeability. Rats were subjected to 2 h of transient middle cerebral artery occlusion and studied at 3 and 48 h of reperfusion, which are crucial times of BBB opening. BBB permeability and ADC values were measured by dynamic contrast-enhanced MRI and diffusion-weighted imaging, respectively. Temporal and spatial analyses of the evolution of BBB permeability and ADC alteration in cortical and subcortical regions were conducted along with the correlation between ADC and BBB permeability data. We found significant increases in BBB leakage and reduction in ADC values between 3 and 48 h of reperfusion. We identified three MR tissue signature models: high K_i and low ADC, high K_i and normal ADC, and normal K_i and low ADC. Over time, areas with normal K_i and low ADC transformed into areas with high K_i. We observed a pattern of lesion evolution where the extent of initial ischemic injury reflected by ADC abnormalities determines vascular integrity. Our results suggest that regions with vasogenic edema alone are not likely to develop low ADC by 48 h and may undergo recovery.     

Preoperative Axillary Staging with 3.0-T Breast MRI: Clinical Value of Diffusion Imaging and Apparent Diffusion Coefficient

The axillary staging in newly diagnosed breast cancer is under major evolution. The aims of this study were to define the diagnostic performance of 3.0-T diffusion-weighted imaging (DWI) in the detection of axillary metastases in newly diagnosed breast cancer, to assess apparent diffusion coefficients (ADCs) for histopathologically confirmed metastatic lymph nodes in a clinical setting. Altogether 52 consecutive breast cancer patients underwent magnetic resonance imaging and DWI in addition to axillary ultrasound. ADCs of axillary lymph nodes were analysed by two breast radiologists and ultrasound-guided core biopsies were taken. In a separate reading by one radiologist two types of region of interests were used for a smaller group of patients. Altogether 56 axillae (121 lymph nodes) were included in the statistical analysis. Metastatic axillae (51.8%) had significantly lower ADCs (p<0.001). Mean ADCs were 0.663–0.676 x 10^-3 mm²/s for the histologically confirmed metastatic LNs and 1.100–1.225 x 10^-3 mm²/s for the benign. The sensitivity, specificity, and accuracy of DWI were 72.4%, 79.6%, and 75.9%, respectively with threshold ADC 0.812 x 10^-3 mm²/s. Region of interest with information on the minimum value increased the diagnostic performance (area under the curve 0.794 vs. 0.619). Even though ADCs are significantly associated with histopathologically confirmed axillary metastases the diagnostic performance of axillary DWI remains moderate and ultrasound-guided core biopsies or sentinel lymph node biopsies cannot be omitted.     

Differentiation between Primary Cerebral Lymphoma and Glioblastoma Using the Apparent Diffusion Coefficient: Comparison of Three Different ROI Methods

Objective

Apparent diffusion coefficients (ADC) can help differentiate between central nervous system (CNS) lymphoma and Glioblastoma (GBM). However, overlap between ADCs for GBM and lymphoma have been reported because of various region of interest (ROI) methods. Our aim is to explore ROI method to provide the most reproducible results for differentiation.

Materials and Methods

We studied 25 CNS lymphomas and 62 GBMs with three ROI methods: (1) ROI₁, whole tumor volume; (2) ROI₂, multiple ROIs; and (3) ROI₃, a single ROI. Interobserver variability of two readers for each method was analyzed by intraclass correlation(ICC). ADCs were compared between GBM and lymphoma, using two-sample t-test. The discriminative ability was determined by ROC analysis.

Results

ADCs from ROI₁ showed most reproducible results (ICC >0.9). For ROI₁, ADC_mean for lymphoma showed significantly lower values than GBM (p = 0.03). The optimal cut-off value was 0.98×10⁻³ mm²/s with 85% sensitivity and 90% specificity. For ROI₂, ADC_min for lymphoma was significantly lower than GBM (p = 0.02). The cut-off value was 0.69×10⁻³ mm²/s with 87% sensitivity and 88% specificity.

Conclusion

ADC values were significantly dependent on ROI method. ADCs from the whole tumor volume had the most reproducible results. ADC_mean from the whole tumor volume may aid in differentiating between lymphoma and GBM. However, multi-modal imaging approaches are recommended than ADC alone for differentiation.     

Correlation of Standardized Uptake Value and Apparent Diffusion Coefficient in Integrated Whole-Body PET/MRI of Primary and Recurrent Cervical Cancer

Background

To evaluate a potential correlation of the maximum standard uptake value (SUV_max) and the minimum apparent diffusion coefficient (ADC_min) in primary and recurrent cervical cancer based on integrated PET/MRI examinations.

Methods

19 consecutive patients (mean age 51.6 years; range 30–72 years) with histopathologically confirmed primary cervical cancer (n = 9) or suspected tumor recurrence (n = 10) were prospectively enrolled for an integrated PET/MRI examination. Two radiologists performed a consensus reading in random order, using a dedicated post-processing software. Polygonal regions of interest (ROI) covering the entire tumor lesions were drawn into PET/MR images to assess SUV_max and into ADC parameter maps to determine ADC_min values. Pearson’s correlation coefficients were calculated to assess a potential correlation between the mean values of ADC_min and SUV_max.

Results

In 15 out of 19 patients cervical cancer lesions (n = 12) or lymph node metastases (n = 42) were detected. Mean SUV_max (12.5±6.5) and ADC_min (644.5±179.7×10⁻⁵ mm²/s) values for all assessed tumor lesions showed a significant but weak inverse correlation (R = −0.342, p<0.05). When subdivided in primary and recurrent tumors, primary tumors and associated primary lymph node metastases revealed a significant and strong inverse correlation between SUV_max and ADC_min (R = −0.692, p<0.001), whereas recurrent cancer lesions did not show a significant correlation.

Conclusions

These initial results of this emerging hybrid imaging technique demonstrate the high diagnostic potential of simultaneous PET/MR imaging for the assessment of functional biomarkers, revealing a significant and strong correlation of tumor metabolism and higher cellularity in cervical cancer lesions.     

Prognostic Significance of Circulating Tumor Cells in Non-Small-Cell Lung Cancer Patients: A Meta-Analysis

Background

The prognostic significance of circulating tumor cells (CTCs) detected in patients with non-small-cell lung cancer (NSCLC) is still inconsistent. We aimed to assess the prognostic relevance of CTCs using a meta-analysis.

Methods

We searched PubMed, Web of Science and EMBASE for relevant studies that assessed the prognostic relevance of CTCs in NSCLC. Statistical analyses were conducted to calculate the summary incidence, odds ratio, relative risks (RRs) and 95% confidence intervals (CIs) using fixed or random-effects models according to the heterogeneity of included studies.

Results

A total of 20 studies, comprising 1576 patients, met the inclusion criteria. In identified studies, CTCs were not correlated with histology (adenocarcinoma vs squamous cell carcinoma) (odds ratio [OR]  =  0.88; 95% confidence interval [CI]: 0.59–1.33; Z = –0.61; P = 0.545). However, pooled analyses showed that CTCs were associated with lymph node metastasis (OR = 2.06; 95% CI: 1.18–3.62; Z = 2.20; P = 0.027) and tumor stage (OR  = 1.95; 95% CI: 1.08–3.54; Z = 2.53; P = 0.011). Moreover, CTCs were significantly associated with shorter overall survival (relative risk [RR]  = 2.19; 95% CI: 1.53–3.12; Z = 4.32; P<0.0001) and progression-free/disease-free survival (RR  = 2.14; 95% CI: 1.36–3.38; Z = 3.28; P<0.0001).

Conclusion

The presence of CTCs indicates a poor prognosis in patients with NSCLC. Further well-designed prospective studies are required to explore the clinical applications of CTCs in lung cancer.     

The Differences in Homocysteine Level between Obstructive Sleep Apnea Patients and Controls: A Meta-Analysis

Background

Studies have reported inconsistent findings regarding the relationship between obstructive sleep apnea (OSA) and homocysteine (HCY) level. This study aimed to assess the difference in plasma HCY level between OSA patients and controls by conducting a meta-analysis of published studies.

Methods

Database of PubMed, SCI, and China National Knowledge Internet (CNKI) were comprehensively searched. Eligible studies regarding plasma HCY level in OSA patients were identified by two independent reviewers. RevMan (version 5.2) and STATA (version 12.0) were employed for data synthesis.

Results

A total of 10 studies involving 432 subjects were included. Meta-analysis showed that plasma HCY levels in OSA group were 3.11 µmol/l higher than that in control group (95% confidence interval: 2.08 to 4.15, P<0.01). Subgroup analysis revealed a more significant differences between OSA patients and controls when average body mass index ≥30 (the total weighted mean difference (WMD) was 3.64), average age<50 (the total WMD was 3.96) and average apnea hypopnea index ≥35 (the total WMD was 4.54).

Conclusions

In this meta-analysis, plasma HCY levels were found to be higher in OSA patients compared to control subjects.     

Temporal Evolution of Parotid Volume and Parotid Apparent Diffusion Coefficient in Nasopharyngeal Carcinoma Patients Treated by Intensity-Modulated Radiotherapy Investigated by Magnetic Resonance Imaging: A Pilot Study

Purpose

To concurrently quantify the radiation-induced changes and temporal evolutions of parotid volume and parotid apparent diffusion coefficient (ADC) in nasopharyngeal carcinoma (NPC) patients treated by intensity-modulated radiotherapy by using magnetic resonance imaging (MRI).

Materials and Methods

A total of 11 NPC patients (9 men and 2 women; 48.7 ± 11.7 years, 22 parotid glands) were enrolled. Radiation dose, parotid sparing volume, severity of xerostomia, and radiation-to-MR interval (RMI) was recorded. MRI studies were acquired four times, including one before and three after radiotherapy. The parotid volume and the parotid ADC were measured. Statistical analysis was performed using SPSS and MedCalc. Bonferroni correction was applied for multiple comparisons. A P value less than 0.05 was considered as statistically significant.

Results

The parotid volume was 26.2 ± 8.0 cm³ before radiotherapy. The parotid ADC was 0.8 ± 0.15 × 10⁻³ mm²/sec before radiotherapy. The parotid glands received a radiation dose of 28.7 ± 4.1 Gy and a PSV of 44.1 ± 12.6%. The parotid volume was significantly smaller at MR stage 1 and stage 2 as compared to pre-RT stage (P < .005). The volume reduction ratio was 31.2 ± 13.0%, 26.1 ± 13.5%, and 17.1 ± 16.6% at stage 1, 2, and 3, respectively. The parotid ADC was significantly higher at all post-RT stages as compared to pre-RT stage reciprocally (P < .005 at stage 1 and 2, P < .05 at stage 3). The ADC increase ratio was 35.7 ± 17.4%, 27.0 ± 12.8%, and 20.2 ± 16.6% at stage 1, 2, and 3, respectively. The parotid ADC was negatively correlated to the parotid volume (R = -0.509; P < .001). The parotid ADC was positively associated with the radiation dose significantly (R² = 0.212; P = .0001) and was negatively associated with RMI significantly (R² = 0.203; P = .00096) significantly. Multiple regression analysis further showed that the post-RT parotid ADC was related to the radiation dose and RMI significantly (R² = 0.3580; P < .0001). At MR stage 3, the parotid volume was negatively associated with the dry mouth grade significantly (R² = 0.473; P < .0001), while the parotid ADC was positively associated with the dry mouth grade significantly (R² = 0.288; P = .015).

Conclusion

Our pilot study successfully demonstrates the concurrent changes and temporal evolution of parotid volume and parotid ADC quantitatively in NPC patients treated by IMRT. Our results suggest that the reduction of parotid volume and increase of parotid ADC are dominated by the effect of acinar loss rather than edema at early to intermediate phases and the following recovery of parotid volume and ADC toward the baseline values might reflect the acinar regeneration of parotid glands.     

Apparent Epigenetic Meiotic Double-Strand-Break Disparity in Saccharomyces cerevisiae: A Meta-Analysis

Previously published, and some unpublished, tetrad data from budding yeast (Saccharomyces cerevisiae) are analyzed for disparity in gene conversion, in which one allele is more often favored than the other (conversion disparity). One such disparity, characteristic of a bias in the frequencies of meiotic double-strand DNA breaks at the hotspot near the His4 locus, is found in diploids that undergo meiosis soon after their formation, but not in diploids that have been cloned and frozen. Altered meiotic DNA breakability associated with altered metabolism-related chromatin states has been previously reported. However, the above observations imply that such differing parental chromatin states can persist through at least one chromosome replication, and probably more, in a common environment. This conclusion may have implications for interpreting changes in allele frequencies in populations.     

qpure: A Tool to Estimate Tumor Cellularity from Genome-Wide Single-Nucleotide Polymorphism Profiles

Tumour cellularity, the relative proportion of tumour and normal cells in a sample, affects the sensitivity of mutation detection, copy number analysis, cancer gene expression and methylation profiling. Tumour cellularity is traditionally estimated by pathological review of sectioned specimens; however this method is both subjective and prone to error due to heterogeneity within lesions and cellularity differences between the sample viewed during pathological review and tissue used for research purposes. In this paper we describe a statistical model to estimate tumour cellularity from SNP array profiles of paired tumour and normal samples using shifts in SNP allele frequency at regions of loss of heterozygosity (LOH) in the tumour. We also provide qpure, a software implementation of the method. Our experiments showed that there is a medium correlation 0.42 (-value = 0.0001) between tumor cellularity estimated by qpure and pathology review. Interestingly there is a high correlation 0.87 (-value 2.2e-16) between cellularity estimates by qpure and deep Ion Torrent sequencing of known somatic KRAS mutations; and a weaker correlation 0.32 (-value = 0.004) between IonTorrent sequencing and pathology review. This suggests that qpure may be a more accurate predictor of tumour cellularity than pathology review. qpure can be downloaded from https://sourceforge.net/projects/qpure/.     

Apparent Diffusion Coefficient (ADC) Value: A Potential Imaging Biomarker That Reflects the Biological Features of Rectal Cancer

Objective

We elected to analyze the correlation between the pre-treatment apparent diffusion coefficient (ADC) and the clinical, histological, and immunohistochemical status of rectal cancers.

Materials and Methods

Forty-nine rectal cancer patients who received surgical resection without neoadjuvant therapy were selected that underwent primary MRI and diffusion-weighted imaging (DWI). Tumor ADC values were determined and analyzed to identify any correlations between these values and pre-treatment CEA or CA19-9 levels, and/or the histological and immunohistochemical properties of the tumor.

Results

Inter-observer agreement of confidence levels from two separate observers was suitable for ADC measurement (k  =  0.775). The pre-treatment ADC values of different T stage tumors were not equal (p  =  0.003). The overall trend was that higher T stage values correlated with lower ADC values. ADC values were also significantly lower for the following conditions: tumors with the presence of extranodal tumor deposits (p  =  0.006) and tumors with CA19-9 levels ≥ 35 g/ml (p  =  0.006). There was a negative correlation between Ki-67 LI and the ADC value (r  =  −0.318, p  =  0.026) and between the AgNOR count and the ADC value (r  =  −0.310, p  =  0.030).

Conclusion

Significant correlations were found between the pre-treatment ADC values and T stage, extranodal tumor deposits, CA19-9 levels, Ki-67 LI, and AgNOR counts in our study. Lower ADC values were associated with more aggressive tumor behavior. Therefore, the ADC value may represent a useful biomarker for assessing the biological features and possible relationship to the status of identified rectal cancers.     

The Correlation between Polybrominated Diphenyl Ethers (PBDEs) and Thyroid Hormones in the General Population: A Meta-Analysis

ObjectiveCertain epidemiological studies have suggested exposure to polybrominated diphenyl ethers (PBDEs) affect the production and secretion of thyroid hormones (TH); however, conflicting results have been reported in different studies. There is not a convincing conclusion about this debate to date.ConclusionThe findings in our meta-analysis indicate the effects of PBDEs on thyroid function may mainly depend on PBDEs exposure and their levels found in serum. The relationship between PBDEs exposure and changes in thyroid function seem to fit an approximate u-shaped curve. These predictions await further verification, namely a prospective longitudinal study.     

Association between Adiponectin Concentrations and Cardiovascular Disease in Diabetic Patients: A Systematic Review and Meta-Analysis

Background

This systematic review and meta-analysis of prospective studies evaluates the association between adiponectin concentrations and risk of cardiovascular disease (CVD) in individuals with diabetes mellitus (DM).

Methods

PubMed and Embase were searched for prospective studies on the association of adiponectin concentrations and risk of CVD up to June 2013. Random-effect model was selected to pool the relative risk (RR) and 95% CI.

Results

Five prospective cohort studies and one nested case-control studies met the included criterion. The estimated summary RR and 95% CI of five prospective cohort studies for type 2 diabetes comparing top vs low tertile of adiponectin concentrations was 0.99 (95% CI: 0.67–1.45), with significant heterogeneity between studies (p = 0.037, I ² = 60.9%). This heterogeneity was explained by one study conducted in Korean.

Conclusions

This study represents the first meta-analysis between adiponectin levels and CVD in diabetic patients and indicated no association was found. This result should be verified further by large sample size, long duration of follow-up, and well-designed prospective clinical trials.     

Simultaneous [18F]FDG-PET/MRI: Correlation of Apparent Diffusion Coefficient (ADC) and Standardized Uptake Value (SUV) in Primary and Recurrent Cervical Cancer

Objectives

Previous non–simultaneous PET/MR studies have shown heterogeneous results about the correlation between standardized uptake values (SUVs) and apparent diffusion coefficients (ADCs). The aim of this study was to investigate correlations in patients with primary and recurrent tumors using a simultaneous PET/MRI system which could lead to a better understanding of tumor biology and might play a role in early response assessment.

Methods

We included 31 patients with histologically confirmed primary (n = 14) or recurrent cervical cancer (n = 17) who underwent simultaneous whole-body ¹⁸F-FDG-PET/MRI comprising DWI. Image analysis was performed by a radiologist and a nuclear physician who identified tumor margins and quantified ADC and SUV. Pearson correlations were calculated to investigate the association between ADC and SUV.

Results

92 lesions were detected. We found a significant inverse correlation between SUV_max and ADC_min (r = -0.532, p = 0.05) in primary tumors as well as in primary metastases (r = -0.362, p = 0.05) and between SUV_mean and ADC_min (r = -0.403, p = 0.03). In recurrent local tumors we found correlations for SUV_max and ADC_min (r = -0.747, p = 0.002) and SUV_mean and ADC_min (r = -0.773, p = 0.001). Associations for recurrent metastases were not significant (p>0.05).

Conclusions

Our study demonstrates the feasibility of fast and reliable measurement of SUV and ADC with simultaneous PET/MRI. In patients with cervical cancer we found significant inverse correlations for SUV and ADC which could play a major role for further tumor characterization and therapy decisions.

Key Point 1

This study investigates the correlation of functional parameters in a simultaneous PET/MRI.

Key Point 2

We found significant inverse correlations between ADC and SUV in cervical carcinoma which could increase knowledge about tumor biology.     

Tumor Necrosis Factor-A Polymorphisms and Colorectal Cancer Risk: A Meta-Analysis

Background and Objectives

Tumor necrosis factor-alpha (TNF-a) was related to inflammation and involved in the development of colorectal cancer. Polymorphisms located in TNF-a promoter region, such as 308G/A and 238G/A, could affect the risk of various types of cancer by regulating TNF-a production. In this study, a meta-analysis was performed to investigate the association between common polymorphisms of TNF-a promoter region and colorectal cancer susceptibility.

Methods

Searching of several databases was performed for all publications on the association between TNF-a polymorphisms and colorectal cancer. Summary odds ratios (ORs) with their 95% confidence intervals (95% CIs) were calculated using random-effects models. Stratified analyses based on ethnicity and control population source were also conducted.

Results

Overall, TNF-a 308A polymorphism showed a significant association with increased risk of colorectal cancer in worldwide populations under homozygote comparison [AA vs. GG, OR (95% CI) = 1.46 (1.07–1.97)] other than heterozygote comparison [AG vs. GG, OR (95% CI) = 1.05 (0.93–1.19)]. TNF-a 238A was not associated with colorectal cancer risk under homozygote or heterozygote comparisons. In stratified analysis, significant association was observed only in Western populations [AA vs. GG, OR (95% CI) = 1.39 (1.01–1.91)] other than in Eastern populations under homozygote comparison. No significant difference was observed between population-based subgroup and hospital-based subgroup.

Conclusions

TNF-a 308A was moderately associated with an increased risk of colorectal cancer in Western populations, and TNF-a 238A polymorphism was not significantly associated with colorectal cancer risk.     

Random Walk Simulation of the MRI Apparent Diffusion Coefficient in a Geometrical Model of the Acinar Tree

Apparent diffusion coefficient (ADC) measurement in the lung using gas magnetic resonance imaging is a promising technique with potential for reflecting changes in lung microstructure. Despite some recent impressive human applications, full interpretation of ADC measures remains an elusive goal, due to a lack of detailed knowledge about the structure dependency of ADC. In an attempt to fill this gap we have performed random walk simulations in a three-dimensional geometrical model of the lung acinus, the distal alveolated sections of the lung tree accounting for ∼90% of the total lung volume. Simulations were carried out adjusting model parameters after published morphological data for the rat peripheral airway system, which predict an ADC behavior as microstructure changes with lung inflation in partial agreement with measured ADCs at different airway pressures. The approach used to relate experimental ADCs to lung microstructural changes does not make any assumption about the cause of the changes, so it could be applied to other scenarios such as chronic obstructive pulmonary disease, lung development, etc. The work presented here predicts numerically for the first time ADC values measured in the lung from independent morphological measures of lung microstructure taken at different inflation stages during the breath cycle.