Can DW-MRI,with its ADC values,be a reliable predictor of biopsy outcome in patients with suspected prostate cancer?

Purpose

To relate the multiparametric magnetic resonance imaging (mp-MRI) of patients with suspect peripheral prostate cancer (PCa) to the results of the subsequent biopsy: in particular to explore whether DWI and ADC can predict the biopsy outcome and to investigate the relation between ADC and Gleason score (GS).

Materials and methods

175 consecutive patients who underwent 1.5 T mp-MRI followed by prostate biopsy were retrospectively analyzed by two independent radiologists. ADC values were measured in the peripheral suspect lesion areas (ADC_SL) and in the contralateral zones (ADC_NSL) obtaining ADC_norm = ADC_SL/ADC_NSL. Results on T2W images, DWI, ADC values, and perfusion studies were matched to their corresponding biopsy.

Results

Negative DWI and T2W had 100% negative predictive value (NPV). When DWI was positive, ADC_SL > 0.90 × 10 > 0.90 × 10^?3 mm²/s (ADC_norm > 0.60) identified by the ROC curve (AUC = 0.80) corresponded to NPV = 85%. In positive biopsies, ADC_SL and ADC_norm decreased significantly from GS = 6 to GS ≥ 8 with Spearman coefficient ρ = ?0.40 and ROC curve AUC = 0.72.

Conclusion

mp-MRI allows a reliable prediction of a negative biopsy through the values of DWI, T2W, and ADC. In positive biopsies, there is a moderate correlation between ADC and the various GS levels.

     

Evaluation of the impact of computed high <Emphasis Type="Italic">b</Emphasis>-value diffusion-weighted imaging on prostate cancer detection

Purpose

The purpose of this study was to compare high b-value (b = 2000 s/mm²) acquired diffusion-weighted imaging (aDWI) with computed DWI (cDWI) obtained using four diffusion models—mono-exponential (ME), intra-voxel incoherent motion (IVIM), stretched exponential (SE), and diffusional kurtosis (DK)—with respect to lesion visibility, conspicuity, contrast, and ability to predict significant prostate cancer (PCa).

Methods

Ninety four patients underwent 3 T MRI including acquisition of b = 2000 s/mm² aDWI and low b-value DWI. High b = 2000 s/mm² cDWI was obtained using ME, IVIM, SE, and DK models. All images were scored on quality independently by three radiologists. Lesions were identified on all images and graded for lesion conspicuity. For a subset of lesions for which pathological truth was established, lesion-to-background contrast ratios (LBCRs) were computed and binomial generalized linear mixed model analysis was conducted to compare clinically significant PCa predictive capabilities of all DWI.

Results

For all readers and all models, cDWI demonstrated higher ratings for image quality and lesion conspicuity than aDWI except DK (p < 0.001). The LBCRs of ME, IVIM, and SE were significantly higher than LBCR of aDWI (p < 0.001). Receiver Operating Characteristic curves obtained from binomial generalized linear mixed model analysis demonstrated higher Area Under the Curves for ME, SE, IVIM, and aDWI compared to DK or PSAD alone in predicting significant PCa.

Conclusion

High b-value cDWI using ME, IVIM, and SE diffusion models provide better image quality, lesion conspicuity, and increased LBCR than high b-value aDWI. Using cDWI can potentially provide comparable sensitivity and specificity for detecting significant PCa as high b-value aDWI without increased scan times and image degradation artifacts.

     

Value of diffusion-weighted MRI and apparent diffusion coefficient measurements for predicting the response of locally advanced rectal cancer to neoadjuvant chemoradiotherapy

Purpose

The aim of our study was to assess the performance value of magnetic resonance imaging (MRI) in the restaging of locally advanced rectal cancer after neoadjuvant chemoradiotherapy (CRT) and in the identification of good vs. poor responders to neoadjuvant therapy.

Materials and Methods

A total of 34 patients with locally advanced rectal cancer underwent MRI prior to and after CRT. T stage and tumor regression grade (TRG) on post-CRT MRI was compared with the pathological staging ypT and TRG. Tumor volume and the apparent diffusion coefficient (ADC) were measured using diffusion-weighted imaging (DWI) before and after neoadjuvant CRT; the percentage of tumor volume reduction and the change of ADC (ΔADC) was also calculated. ADC parameters and the percentage of tumor volume reduction were correlated to histopathological results. The diagnostic performance of ADC and volume reduction to assess tumor response was evaluated by calculating the area under the ROC curve and the optimal cut-off values.

Results

A significant correlation between the T stage and the TRG defined in DW-MRI after CRT and the ypT and the TRG observed on the surgical specimens was found (p = 0.001; p < 0.001). The mean post-CRT ADC and ΔADC in responder patients was significantly higher compared to non-responder ones (p = 0.001; p = 0.01). Furthermore, the mean post-CRT ADC values were significantly higher in tumors with T-downstage (p = 0.01).

Conclusion

DW-MRI may have a significant role in the restaging and in the evaluation of post-CRT response of locally advanced rectal cancer. Quantitative analysis of DWI through ADC map may result in a promising noninvasive tool to evaluate the response to therapy.

     

Can diffusion-weighted magnetic resonance imaging predict tumor recurrence of uterine cervical cancer after concurrent chemoradiotherapy?

Purpose

To retrospectively investigate the utility of diffusion-weighted imaging (DWI) for predicting clinical outcome after concurrent chemoradiotherapy (CCRT) in uterine cervical cancer.

Materials and methods

Seventy-four consecutive patients with biopsy-proven cervical cancer who received CCRT underwent DWI at 3T. All patients had MR examinations before therapy (preTx) and at 4 weeks of initiating therapy (midTx). At each point, ADC (apparent diffusion coefficient) was measured in the tumors and ADC change between preTx and midTx were also calculated. For predicting tumor recurrence, MR variables and clinical variables were evaluated and the results were compared.

Results

During a mean follow-up of 32.1 months, tumor recurrence developed in 15 (20%) patients: local recurrence (n = 7), distant metastasis (n = 5), and both (n = 3). MidTx tumor ADCs and tumor ADC changes between preTx and midTx were significantly different between the recurrence and non-recurrence groups (P < 0.05), while preTx tumor ADCs were not significantly different between the groups (P = 0.892). Univariate analysis revealed that histologic type, stage, preTx tumor size and volume, and tumor ADC change were significantly related to tumor recurrence (all P < 0.05). However, on multivariate analysis, tumor ADC changes [hazard ratio (HR) 0.886; 95% confidence interval (CI) 0.836–0.940; P = 0.001] and histological type (HR 6.063; 95% CI 1.404–26.187; P = 0.016) were the significant independent predictors of tumor recurrence.

Conclusion

Tumor ADC changes between preTx and midTx might be a useful biomarker for the prediction of cervical cancer recurrence after CCRT.

     

Diffusion Profiling <Emphasis Type="Italic">via</Emphasis> a Histogram Approach Distinguishes Low-grade from High-grade Meningiomas,Can Reflect the Respective Proliferative Potential and Progesterone Receptor Status

Purpose

Presurgical grading, estimation of growth kinetics, and other prognostic factors are becoming increasingly important for selecting the best therapeutic approach for meningioma patients. Diffusion-weighted imaging (DWI) provides microstructural information and reflects tumor biology. A novel DWI approach, histogram profiling of apparent diffusion coefficient (ADC) volumes, provides more distinct information than conventional DWI. Therefore, our study investigated whether ADC histogram profiling distinguishes low-grade from high-grade lesions and reflects Ki-67 expression and progesterone receptor status.

Procedures

Pretreatment ADC volumes of 37 meningioma patients (28 low-grade, 9 high-grade) were used for histogram profiling. WHO grade, Ki-67 expression, and progesterone receptor status were evaluated. Comparative and correlative statistics investigating the association between histogram profiling and neuropathology were performed.

Results

The entire ADC profile (p10, p25, p75, p90, mean, median) was significantly lower in high-grade versus low-grade meningiomas. The lower percentiles, mean, and modus showed significant correlations with Ki-67 expression. Skewness and entropy of the ADC volumes were significantly associated with progesterone receptor status and Ki-67 expression. ROC analysis revealed entropy to be the most accurate parameter distinguishing low-grade from high-grade meningiomas.

Conclusions

ADC histogram profiling provides a distinct set of parameters, which help differentiate low-grade versus high-grade meningiomas. Also, histogram metrics correlate significantly with histological surrogates of the respective proliferative potential. More specifically, entropy revealed to be the most promising imaging biomarker for presurgical grading. Both, entropy and skewness were significantly associated with progesterone receptor status and Ki-67 expression and therefore should be investigated further as predictors for prognostically relevant tumor biological features. Since absolute ADC values vary between MRI scanners of different vendors and field strengths, their use is more limited in the presurgical setting.

     

Diffusion-weighted imaging of hepatocellular carcinomas: a retrospective analysis of correlation between apparent diffusion coefficients and histological grade

Purpose

To define correlations between the pathological grades of hepatocellular carcinomas (HCCs) and apparent diffusion coefficients (ADCs) derived using breath-holding diffusion-weighted imaging (BH-DWI).

Methods

We retrospectively evaluated 94 patients (105 lesions) with pathologically proved HCC who underwent hepatic DWI on a 3.0-T MR platform. HCCs were divided into five groups: well-differentiated (n = 10), well-to-moderately differentiated (n = 11), moderately differentiated (n = 51), moderately to poorly differentiated (n = 20), and poorly differentiated (n = 13) groups. The ADCs of carcinomas across different histological grades were compared by one-way analysis of variance. Spearman’s rank correlation test was used to analyze correlations between the degree of histopathological differentiation and ADC. Results were corrected for multiple comparisons using the Bonferroni correction.

Results

The BH technique yielded ADC values that differed significantly by the extent of differentiation (F = 8.392, p < 0.001). A significant negative correlation was found between the extent of differentiation and ADCs (r = ?0.462, p < 0.001). The mean ADC values of poorly differentiated HCCs were significantly lower than the well-, well-to-moderately, moderately, and moderately to poorly differentiated HCCs (p values were <0.001, <0.001, 0.003, and 0.031, respectively).

Conclusion

ADC values obtained with BH-DWI may be of importance to non-invasively predict HCC tumor differentiation, and the extent of histological HCC differentiation was inversely correlated with ADC values.

     

Diffusion-weighted and hepatobiliary phase gadoxetic acid-enhanced quantitative MR imaging for identification of complete pathologic response in colorectal liver metastases after preoperative chemotherapy

Purpose

To evaluate the diagnostic performance of diffusion-weighted imaging (DWI) and gadoxetic acid-enhanced magnetic resonance imaging (MRI) to differentiate colorectal liver metastasis (CRLM) with complete pathologic response from those with incomplete response in patients treated with preoperative chemotherapy.

Methods

Gadoxetic acid-enhanced liver MRI and DWI were performed after completion of preoperative chemotherapy in patients with CRLM scheduled for liver resection. Metastases were classified as those with complete pathologic response (CR-CRLM) or incomplete response (IR-CRLM) according to postsurgical histopathology. Quantitative analysis was performed on non-contrast-enhanced images and hepatobiliary phase images following gadoxetic acid administration. Apparent diffusion coefficient values (ADC), normalized relative enhancement (NRE), and relative signal intensity difference (RSID) along with their diagnostic measures for detection of CR-CRLM were calculated for all lesions.

Results

In 23 patients, 10 CR-CRLM and 35 IR-CRLM (mean diameter, 21.2 mm) were evaluated. In CR-CRLM, ADC was significantly higher after exclusion of the outliers (p = 0.030); and RSID was significantly lower (p = 0.008). Combined indices range of ADC = 1.25?1.9 × 10^?3 mm²/s, NRE = 0?35% and RSID <120 had 60% sensitivity and 100% specificity for detection of CR-CRLM.

Conclusion

DWI and gadoxetic acid-enhanced MRI appear promising for the detection of CRLM with complete response to preoperative chemotherapy. This could have significant implications for liver resection planning after preoperative chemotherapy.

     

Correlation Between Aquaporin 4 Expression and Different DWI Parameters in Grade I Meningioma

Purpose

Diffusion-weighted imaging (DWI) measures water diffusion in biological tissues. Cellular water transport depends on aquaporins (AQPs). The expression of aquaporins might differ in several pathologic disorders. Therefore, the aim of this study was to evaluate the associations between AQP4 expression and different DWI parameters in meningioma.

Procedures

Twenty-three patients with meningioma grade I were included in this retrospective study. DWI was obtained with three b values (0; 500; 1000) using a 1.5-T device. ADC_mean, ADC_min, ADC_max, and true diffusion coefficients (D) were obtained in every patient. Aquaporin 4 expression was quantified immunohistochemically in four immunoreactivity levels.

Results

The estimated DWI parameters (mean value ± standard deviation, 10^?3 mm² s^?1) of the tumors were as follows: ADC_min 0.67 ± 0.16, ADC_mean 0.94 ± 0.23, ADC_max 1.29 ± 0.50, and D 0.65 ± 0.23. The mean level of the AQP4 expression was 2.02 ± 0.75 points. A statistically significant correlation between AQP4 expression and ADC_max was identified (r = 0.508, p = 0.013). No significant correlations between AQP4 and other DWI parameters were found.

Conclusions

A clear correlation between AQP4 expression and ADC_max values in grade I meningioma was identified. There were no significant correlations between AQP4 expression and other DWI parameters, such as ADC_min, ADC_mean, and D.

     

A Randomized Trial Investigating the Pharmacokinetics,Pharmacodynamics, and Safety of Subcutaneous Semaglutide Once-Weekly in Healthy Male Japanese and Caucasian Subjects

Introduction

Semaglutide is a glucagon-like peptide-1 analogue for once-weekly subcutaneous treatment of type 2 diabetes. This trial compared the pharmacokinetics, pharmacodynamics, and safety of semaglutide in Japanese and Caucasian subjects.

Methods

In this single-center, double-blind, parallel-group, 13-week trial, 44 healthy male subjects (22 Japanese, 22 Caucasian) were randomized within each race to semaglutide 0.5 mg (n = 8), 1.0 mg (n = 8), placebo 0.5 mg (n = 3) or 1.0 mg (n = 3). The primary endpoint was semaglutide exposure at steady state [area under the curve (AUC_0–168h)].

Results

Steady-state exposure of semaglutide was similar for both populations: AUC_0–168h estimated race ratio (ERR), Japanese/Caucasian: 0.5 mg, 1.06; 1.0 mg, 0.99; maximum concentration (C_max) ERR: 0.5 mg, 1.06; 1.0 mg, 1.02. Exposure after the first dose (0.25 mg) was slightly higher in Japanese versus Caucasian subjects (AUC_0–168h ERR 1.11; C_max ERR 1.14). Dose-dependent increases in AUC_0–168h and C_max occurred in both populations. Accumulation was as expected, based on the half-life (t_1/2, ~ 1 week) and dosing interval of semaglutide. Significant body weight reductions were observed with semaglutide 0.5 mg and 1.0 mg in Japanese (both p ≤ 0.05) and Caucasian (both p ≤ 0.05) subjects versus placebo. No new safety issues were identified.

Conclusions

The pharmacokinetic, pharmacodynamic, and safety profiles of semaglutide were similar in Japanese and Caucasian subjects, suggesting that no dose adjustment is required for the clinical use of semaglutide in Japanese subjects.

Funding

Novo Nordisk A/S, Denmark.

Trial registration

ClinicalTrials.gov identifier NCT02146079. Japanese trial registration number JapicCTI-142550.

     

A Single-Dose,Crossover-Design Bioequivalence Study Comparing Two Nicotine Gum Formulations in Healthy Subjects

Introduction

Nicotine replacement therapy (NRT) benefits smokers who wish to quit; nicotine gum represents one NRT. New formulations of nicotine gum have been developed to consider consumer preferences and needs. A new mint-flavored nicotine gum with a different texture was developed that may provide a more appealing taste and chewing experience. This study evaluated this new nicotine gum (2 and 4 mg strengths) for bioequivalence versus the original flavor sugar-free nicotine gum at corresponding dosages.

Methods

All subjects randomized in this crossover study received a single dose of all treatments, i.e., 2 and 4 mg doses of test and reference gums, separated by 2–7 days of washout between treatments. Subjects’ maximal plasma nicotine concentration (C_max) and extent of nicotine absorption (AUC_0–t) following the administration of each treatment were calculated from plasma nicotine concentrations. Ratios of test/reference for C_max and AUC_0–t were calculated to evaluate bioequivalence between the two products.

Results

Both 2 and 4 mg doses of the new mint-flavored nicotine gum were bioequivalent to the dose-matched reference product as determined by the ratio of the geometric means and their 90% confidence intervals for C_max and AUC_0–t as well as secondary pharmacokinetic parameters. The safety profiles of the test and reference gums were similar; all treatments were well tolerated.

Conclusions

A new mint-flavored nicotine gum with modified taste and texture is bioequivalent to the original flavor sugar-free nicotine gum at both the 2 and 4 mg dosage strengths and has a similar safety profile.

Funding

GlaxoSmithKline.

Trial Registration

ClinicalTrials.gov identifier NCT01847443.

     

Value of diffusion-weighted MR imaging in the diagnosis of lymph node metastases in patients with cholangiocarcinoma

Purpose

To evaluate diffusion-weighted MR imaging (DWI) in the diagnosis of lymph node metastases in patients with cholangiocarcinoma.

Methods

In 24 patients with cholangiocarcinoma, MR imaging of the upper abdomen was performed prior to surgery at 1.5 T using a respiratory-triggered single-shot echo-planar imaging (SSEPI) sequence (b values: 50, 300, and 600 s/mm²). ADC (apparent diffusion coefficient) values and diameters of regional lymph nodes (LN) were determined. Subsequently, in all patients, surgical exploration and/or resection of the primary tumor and regional LN dissection were performed. Imaging results were correlated with results of histopathologic analysis. ADC values and diameters of benign and malignant LN were compared using the Mann–Whitney U test. In addition, a ROC (receiver operating characteristic curve) analysis was performed.

Results

The mean ADC value (×10^?3 mm²/s) of metastatic LN (1.21 ± 0.15) was significantly lower than that of benign LN (1.62 ± 0.33, p < 0.001) while there was no significant difference in the mean diameter of malignant (16.8 ± 5.4 mm) and benign LN (14.1 ± 4.0 mm; p = 0.09). Using an ADC value of 1.25 × 10^?3 mm²/s as threshold, 91.4% of LN were correctly classified as benign or malignant with a sensitivity/specificity of 83.3%/92.8% and a positive/negative predictive value of 66.7%/96.7%. The area under the ROC curve was 0.93.

Conclusion

DWI using a respiratory-triggered SSEPI sequence, according to our preliminary experience, is a promising imaging modality in the differentiation of benign and malignant LN in patients with cholangiocarcinoma.

     

Restriction spectrum imaging improves MRI-based prostate cancer detection

Purpose

To compare the diagnostic performance of restriction spectrum imaging (RSI), with that of conventional multi-parametric (MP) magnetic resonance imaging (MRI) for prostate cancer (PCa) detection in a blinded reader-based format.

Methods

Three readers independently evaluated 100 patients (67 with proven PCa) who underwent MP-MRI and RSI within 6 months of systematic biopsy (N = 67; 23 with targeting performed) or prostatectomy (N = 33). Imaging was performed at 3 Tesla using a phased-array coil. Readers used a five-point scale estimating the likelihood of PCa present in each prostate sextant. Evaluation was performed in two separate sessions, first using conventional MP-MRI alone then immediately with MP-MRI and RSI in the same session. Four weeks later, another scoring session used RSI and T2-weighted imaging (T2WI) without conventional diffusion-weighted or dynamic contrast-enhanced imaging. Reader interpretations were then compared to prostatectomy data or biopsy results. Receiver operating characteristic curves were performed, with area under the curve (AUC) used to compare across groups.

Results

MP-MRI with RSI achieved higher AUCs compared to MP-MRI alone for identifying high-grade (Gleason score greater than or equal to 4 + 3=7) PCa (0.78 vs. 0.70 at the sextant level; P < 0.001 and 0.85 vs. 0.79 at the hemigland level; P = 0.04). RSI and T2WI alone achieved AUCs similar to MP-MRI for high-grade PCa (0.71 vs. 0.70 at the sextant level). With hemigland analysis, high-grade disease results were similar when comparing RSI + T2WI with MP-MRI, although with greater AUCs compared to the sextant analysis (0.80 vs. 0.79).

Conclusion

Including RSI with MP-MRI improves PCa detection compared to MP-MRI alone, and RSI with T2WI achieves similar PCa detection as MP-MRI.

     

ADC Histogram Analysis of Cervical Cancer Aids Detecting Lymphatic Metastases—a Preliminary Study

Purpose

Apparent diffusion coefficient (ADC) histogram analysis has been used to some extent in cervical cancer (CC) to distinguish between low-grade and high-grade tumors. Although this differentiation is undoubtedly helpful, it would be even more crucial in the presurgical setting to determine whether a tumor already gained the potential to metastasize via the lymphatic system. So far, no studies investigated the potential of 3T ADC histogram analysis in CC to differentiate between nodal-positive and nodal-negative entities. Therefore, the principal aim of our study was to investigate the potential of 3T ADC histogram analysis to differentiate between CC with and without lymph node metastasis. The second aim was to elucidate possible differences in ADC histogram parameters between CC with limited vs. advanced tumor stages and well-differentiated vs. undifferentiated lesions. Finally, correlations of p53 expression and Ki-67 index with ADC parameters were analyzed.

Procedures

Eighteen female patients (mean age 55.4 years, range 32–79 years) with histopathologically confirmed cervical squamous cell carcinoma of the uterine cervix were prospectively enrolled. Tumor stages, tumor grading, status of metastatic dissemination, Ki67-index, and p53 expression were assessed in these patients. Diffusion weighted imaging (DWI) was obtained in a 3T scanner using the following b values: b0 and b1000 s/mm².

Results

Group comparisons using Mann-Whitney U test revealed the following findings: nodal-positive CC had statistically significant lower ADC parameters (ADCmin, ADCmean, median ADC, Mode, p10, p25, p75, and p90) in comparison to nodal-negative CC (all p < 0.05). ADCentropy was significantly elevated (p = 0.046) in tumors with advanced T stages (T3/4) compared to tumors with limited T stage (T2). ADCmin values were different in a statistically significant manner comparing G1/G2 and G3 tumors (40.45 ± 18.63 vs. 65.0 ± 23.63 × 10–5 mm2 s^?1, p = 0.035). Furthermore, Spearman Rho calculation identified an inverse correlation between ADCentropy and p53 expression (r = ?0.472, p = 0.048).

Conclusion

The main finding of our study is the discriminability of nodal-positive from nodal-negative CC using ADC histogram analysis in 3T DWI. This information is crucial for the gynecological surgeon to identify the optimal treatment strategy for patients suffering from CC. Furthermore, ADCentropy was identified as a potential imaging biomarker for tumor heterogeneity and might be able to indicate further molecular changes like loss of p53 expression, which is associated with EMT and consequentially indicates a poor prognosis in CC. Finally, our study confirmed the findings of previous works, which indicated that histogram analysis of ADC maps can distinguish between low-grade and high-grade CC. In conclusion, it can be stated that ADC histogram analysis provides additional, prognostically important information on tumor biology in CC.

     

Selecting Tumor-Specific Molecular Targets in Pancreatic Adenocarcinoma: Paving the Way for Image-Guided Pancreatic Surgery

Purpose

The purpose of this study was to identify suitable molecular targets for tumor-specific imaging of pancreatic adenocarcinoma.

Procedures

The expression of eight potential imaging targets was assessed by the target selection criteria (TASC)—score and immunohistochemical analysis in normal pancreatic tissue (n?=?9), pancreatic (n?=?137), and periampullary (n?=?28) adenocarcinoma.

Results

Integrin α_vβ₆, carcinoembryonic antigen (CEA), epithelial growth factor receptor (EGFR), and urokinase plasminogen activator receptor (uPAR) showed a significantly higher (all p?<?0.001) expression in pancreatic adenocarcinoma compared to normal pancreatic tissue and were confirmed by the TASC score as promising imaging targets. Furthermore, these biomarkers were expressed in respectively 88 %, 71 %, 69 %, and 67 % of the pancreatic adenocarcinoma patients.

Conclusions

The results of this study show that integrin α_vβ₆, CEA, EGFR, and uPAR are suitable targets for tumor-specific imaging of pancreatic adenocarcinoma.

     

Added value of diffusion-weighted imaging to MR cholangiopancreatography for the diagnosis of bile duct dilatations

Purpose

To investigate the added value of diffusion-weighted imaging (DWI) when used with conventional T2-weighted magnetic resonance (MR) imaging (T2WI) and MR cholangiopancreatography (MRCP) for diagnosing bile duct dilatations.

Methods

Our institutional review board approved this retrospective study protocol and waived the informed consent requirement. The study included 151 consecutive patients (70 men, 81 women) with intra- and/or extra-hepatic bile duct dilatation examined using MR imaging. Two radiologists independently and randomly reviewed 3 image sets (A: MRCP and T2WI; B: DWI; and C: combined T2WI, MRCP, and DWI) at different occasions to differentiate between malignancy, biliary lithiasis, and benign dilatation. The sensitivity, specificity, and diagnostic accuracy of these imaging sets were calculated and compared.

Results

For both readers, combined T2WI, MRCP, and DWI exhibited significantly higher sensitivity and diagnostic accuracy for malignant dilatation, compared with conventional T2WI and MRCP (P < 0.01 for both readers). However, DWI did not significantly affect the sensitivity and diagnostic accuracy for biliary lithiasis or benign dilatation.

Conclusion

The addition of DWI to T2WI and MRCP sequences yields significantly higher sensitivity and diagnostic accuracy when examining bile duct dilatations, particularly malignant dilatations.

     

Effect of synbiotic therapy on the incidence of ventilator associated pneumonia in critically ill patients: a randomised,double-blind,placebo-controlled trial

Objective

To investigate the effect of enteral Synbiotic 2000 FORTE^® (a mixture of lactic acid bacteria and fibre) on the incidence of ventilator associated pneumonia (VAP) in critically ill patients.

Design

Prospective, randomised, double blind, placebo controlled trial.

Setting

Tertiary referral centre, general Adult Intensive Care Unit (ICU).

Patients and participants

259 enterally fed patients requiring mechanical ventilation for 48 h or more were enrolled.

Intervention

All patients were enterally fed as per a standard protocol and randomly assigned to receive either synbiotic 2000 FORTE^® (twice a day) or a cellulose-based placebo for a maximum of 28 days.

Measurements and results

Treatment group (n = 130) was well matched with placebo group (n = 129) for age (mean 49.5 and 50 years, respectively) and APACHE II score (median 17 for both). Oropharyngeal microbial flora and colonisation rates were unaffected by synbiotics. The overall incidence of VAP was lower than anticipated (11.2%) and no statistical difference was demonstrated between groups receiving synbiotic and placebo in the incidence of VAP (9 and 13%, P = 0.42), VAP rate per 1,000 ventilator days (13 and 14.6, P = 0.91) or hospital mortality (27 and 33%, P = 0.39), respectively.

Conclusions

Enteral administration of Synbiotic 2000 FORTE^® has no statistically significant impact on the incidence of VAP in critically ill patients.

     

Bioluminescence Imaging of Colonization and Clearance Dynamics of <Emphasis Type="Italic">Brucella Suis</Emphasis> Vaccine Strain S2 in Mice and Guinea Pigs

Purpose

The goal of this study was to develop a plasmid-based lux bio-reporter for use to obtain in vivo images of Brucella suis vaccine strain 2 (B.suis S2) infection with high resolution and good definition.

Procedures

The pBBR-lux (pBBR1MCS-2-lxCDABE) plasmid that carries the luxCDABE operon was introduced into B. suis S2 by electroporation yielding B. suis S2-lux. The spatial and temporal transit of B. suis S2 in mice and guinea pigs was monitored by bioluminescence imaging.

Results

The plasmid pBBR-lux is stable in vivo and does not appear to impact the virulence or growth of bacteria. This sensitive luciferase reporter could represent B. suis S2 survival in real time. B. suis S2 mainly colonized the lungs, liver, spleen, and uterus in mice and guinea pigs as demonstrated by bioluminescence imaging.

Conclusion

The plasmid-based lux bioreporter strategy can be used to obtain high resolution in vivo images of B. suis S2 infection in mice and guinea pigs.

     

<Emphasis Type="Italic">L</Emphasis><Subscript><Emphasis Type="Italic">p</Emphasis></Subscript> Regularization for Bioluminescence Tomography Based on the Split Bregman Method

Purpose

Bioluminescence tomography (BLT) is a promising in vivo optical imaging technique in preclinical research at cellular and molecular levels. The problem of BLT reconstruction is quite ill-posed and ill-conditioned. In order to achieve high accuracy and efficiency for its inverse reconstruction, we proposed a novel approach based on L _p regularization with the Split Bregman method.

Procedures

The diffusion equation was used as the forward model. Then, we defined the objective function of L _p regularization and developed a Split Bregman iteration algorithm to optimize this function. After that, we conducted numerical simulations and in vivo experiments to evaluate the accuracy and efficiency of the proposed method.

Results

The results of the simulations indicated that compared with the conjugate gradient and iterative shrinkage methods, the proposed method is more accurate and faster for multisource reconstructions. Furthermore, in vivo imaging suggested that it could clearly distinguish the viable and apoptotic tumor regions.

Conclusions

The Split Bregman iteration method is able to minimize the L _p regularization problem and achieve fast and accurate reconstruction in BLT.

     

Is there an added value of a hepatobiliary phase with gadoxetate disodium following conventional MRI with an extracellular gadolinium agent in a single imaging session for detection of primary hepatic malignancies?

Purpose

To determine added value of hepatobiliary phase (HBP) using gadoxetate disodium compared to MRI with extracellular gadolinium-based contrast agent (GBCA) for detection of primary hepatic malignancies in a single imaging session.

Materials and methods

IRB approved this HIPAA compliant retrospective study. Within 90 days of resection or liver transplant, thirty patients underwent MRI with extracellular GBCA followed by separate injection of gadoxetate for HBP. Two sets of images were reviewed: Set #1—unenhanced and enhanced images with an extracellular GBCA and set #2—with addition of HBP. Data were analyzed in two groups, cases with hepatocellular carcinoma (HCC) only and cases with either HCC and/or cholangiocarcinoma. Observer diagnostic accuracy (A_z), sensitivity, and specificity were calculated.

Results

14/30 subjects had HCC (46%, CI 28–66%), 2/30 (2%, CI 1–22%) cholangiocarcinoma, and 14/30 (46%, CI 28–66%) no malignancy. There was no significant change in A _z value with addition of gadoxetate in the detection of HCC (range 0.84–0.97 set #1 and 0.85–0.97 set #2, p > 0.05). Sensitivity and specificity showed no significant differences (p > 0.05) between the image sets for all readers. When stratified by lesion size, there was no significant difference in accuracy, sensitivity, or specificity for any reader (p > 0.05).

Conclusion

When compared to extracellular GBCA, gadoxetate HBP imaging does not result in a significant difference in accuracy or sensitivity in diagnosis of HCC or cholangiocarcinoma and may result in a decrease in specificity.

     

The Role of Intravoxel Incoherent Motion MRI in Predicting Early Treatment Response to Chemoradiation for Metastatic Lymph Nodes in Nasopharyngeal Carcinoma

Introduction

Pilot studies have suggested potential clinical applications for intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) in head and neck cancers. This study aimed to characterize metastatic lymph nodes using IVIM MRI, and to evaluate the role of IVIM MRI in the prediction of the early treatment response of lymph node metastasis from nasopharyngeal carcinoma (NPC).

Methods

A total of 122 patients with metastatic lymph nodes from NPC underwent two MRI examinations, pre-treatment and post-treatment (at 4 weeks and at ≥2 years from the end of chemoradiotherapy). Treatment response was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1. Differences in the initial IVIM parameters [pure molecular diffusion (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f)] between nodes with a partial response (PR) and a complete response (CR) were analyzed in 102 patients after the exclusion of 20.

Results

The initial D*, D, and apparent diffusion coefficient (ADC) did not reveal a significant difference between nodes showing a PR or a CR. The mean initial f value was significantly higher in patients with a PR relative to patients with a CR (p = 0.003), and its sensitivity and specificity in predicting treatment response to chemoradiotherapy were 86.7% and 100%, respectively.

Conclusions

The present study indicated that the initial f value may be more accurate than the initial D*, D, and ADC in the early prediction of treatment response to chemoradiotherapy for metastatic lymph nodes in patients with NPC.