Therapeutic Hypothermia Modifies Perinatal Asphyxia-Induced Changes of the Corpus Callosum and Outcome in Neonates

What Is Known about this Subject?

Diffusion-weighted MRI has demonstrated changes in the corpus callosum of term neonates with perinatal asphyxia. The severity of cerebral changes demonstrated using diffusion-weighted MRI is difficult to assess without measuring values of the Apparent Diffusion Coefficient (ADC).

What Is New?

ADC values of the anterior part of the corpus callosum are slightly higher than of the posterior part in full term infants with perinatal asphyxia. Low ADC values of the corpus callosum were associated with an adverse outcome in infants with perinatal asphyxia. In infants treated with hypothermia lower ADC values than with normothermia were associated with a poor outcome, supporting neuroprotective effects of hypothermia

Background

Using MRI, changes can be detected in the corpus callosum (CC) following perinatal asphyxia which are associated with later neurodevelopmental outcome.

Aim

To study the association between the apparent diffusion coefficient of water (ADC) in the CC on MRI in neonates with perinatal asphyxia and neurodevelopmental outcome at 18 months of age.

Subjects, Methods

Of 121 infants 32 (26%) died and 13 (11%) survived with an adverse neurological outcome. Sixty-five (54%) received therapeutic hypothermia. MRI was performed within 7 days after birth using a 1.5 T or 3.0 T system, and ADC values were measured in the anterior and posterior CC. The association between ADC and composite outcome (death or abnormal neurodevelopment) was analyzed for both normothermia and hypothermia cases using receiver operating characteristics.

Results

ADC values of the posterior CC were lower than of the anterior part (mean difference 0.050 x 10^-3 mm²/s, p<0.001). Field strength did not affect ADC values. ADC values of the posterior part of the CC were significantly lower in infants with basal ganglia/thalamus or near total brain injury (p<0.001). Lower ADC values were associated with an adverse outcome, but cut-off levels were lower after hypothermia (1.024 x 10^-3 mm²/s vs 0.969 x 10^-3 mm²/s)

Conclusion

Low ADC values of the posterior part of the corpus callosum are associated with an adverse outcome in term or near term neonates with perinatal asphyxia. Therapeutic hypothermia slightly modifies this association, showing that lower values were needed for an adverse outcome.     

A New Atlas Localization Approach for Subthalamic Nucleus Utilizing Chinese Visible Human Head Datasets

Objective

To study the possibility of Chinese visible human (CVH) head datasets as brain atlas for locating the subthalamic nucleus (STN) before deep brain stimulation (DBS) surgery.

Methods

Optimal head axial and coronal 3.0T, T2-weighted magnetic resonance images (MRI) of 30 patients were obtained. Cross-sectional head images of four CVH head datasets were chosen to establish an average CVH model. All MRI sequences were registered to the CVH model via fiducials in X-, Y-, and Z-direction, respectively, within the same stereotactic space. The correlations between red nucleus (RN) and fiducials, the accuracy of MRI-to-CVH registration, and the coordinate value differences of RN gravity center between MRI and CVH were tested.

Results

The mean gravity center coordinate values and ranges of STN in CVH were measured; The X coordinate value of RN positively correlates with the most anterior point of putamen(PU-A), the lateral edges of putamens (PU-L), and width of the third ventricle, negatively correlated with the patients’ age; The minimal mean errors were when no fiducials were used when locating RN between the MRI and the CVH average model; There were no significant differences of RN in X- and Y-direction between MRI sequences and CVH.

Conclusion

CVH head datasets can be used as brain atlas for Chinese STN localization. Moreover, average coordinate values of the gravity center and the ranges of STN in CVH can be considered as references for locating STN.     

Turbulent Kinetic Energy Measurement Using Phase Contrast MRI for Estimating the Post-Stenotic Pressure Drop: In Vitro Validation and Clinical Application

Background

Although the measurement of turbulence kinetic energy (TKE) by using magnetic resonance imaging (MRI) has been introduced as an alternative index for quantifying energy loss through the cardiac valve, experimental verification and clinical application of this parameter are still required.

Objectives

The goal of this study is to verify MRI measurements of TKE by using a phantom stenosis with particle image velocimetry (PIV) as the reference standard. In addition, the feasibility of measuring TKE with MRI is explored.

Methods

MRI measurements of TKE through a phantom stenosis was performed by using clinical 3T MRI scanner. The MRI measurements were verified experimentally by using PIV as the reference standard. In vivo application of MRI-driven TKE was explored in seven patients with aortic valve disease and one healthy volunteer. Transvalvular gradients measured by MRI and echocardiography were compared.

Results

MRI and PIV measurements of TKE are consistent for turbulent flow (0.666 < R² < 0.738) with a mean difference of −11.13 J/m³ (SD = 4.34 J/m³). Results of MRI and PIV measurements differ by 2.76 ± 0.82 cm/s (velocity) and −11.13 ± 4.34 J/m³ (TKE) for turbulent flow (Re > 400). The turbulence pressure drop correlates strongly with total TKE (R² = 0.986). However, in vivo measurements of TKE are not consistent with the transvalvular pressure gradient estimated by echocardiography.

Conclusions

These results suggest that TKE measurement via MRI may provide a potential benefit as an energy-loss index to characterize blood flow through the aortic valve. However, further clinical studies are necessary to reach definitive conclusions regarding this technique.     

Positron Emission Tomography and Magnetic Resonance Imaging of the Brain in Fabry Disease: A Nationwide,Long-Time,Prospective Follow-Up

Background

Fabry disease is a rare metabolic glycosphingolipid storage disease caused by deficiency of the lysosomal enzyme α-galactosidase A—leading to cellular accumulation of globotriasylceramide in different organs, vessels, tissues, and nerves. The disease is associated with an increased risk of cerebrovascular disease at a young age in addition to heart and kidney failure.

Objective

The objective of this study was to assess brain function and structure in the Danish cohort of patients with Fabry disease in a prospective way using 18-fluoro-deoxyglucose (F-18 FDG) positron emission tomography (PET) and magnetic resonance imaging (MRI).

Patients

Forty patients with Fabry disease (14 males, 26 females, age at inclusion: 10–66 years, median: 39 years) underwent a brain F-18-FDG-PET-scan at inclusion, and 31 patients were followed with FDG-PET biannually for up to seven years. All patients (except one) had a brain MRI-scan at inclusion, and 34 patients were followed with MRI biannually for up to nine years.

Image Analysis

The FDG-PET-images were inspected visually and analysed using a quantitative 3-dimensional stereotactic surface projection analysis (Neurostat). MRI images were also inspected visually and severity of white matter lesions (WMLs) was graded using a visual rating scale.

Results

In 28 patients brain-FDG-PET was normal; in 23 of these 28 patients brain MRI was normal—of the remaining five patients in this group, four patients had WMLs and one patient never had an MRI-scan. In 10 patients hypometabolic areas were observed on brain-FDG-PET; all of these patients had cerebral infarcts/hemorrhages visualized on MRI corresponding to the main hypometabolic areas. In two patients brain-FDG-PET was ambiguous, while MRI was normal in one and abnormal in the other.

Conclusion

Our data indicated that, in patients with Fabry disease, MRI is the preferable clinical modality—if applicable—when monitoring cerebral status, as no additional major brain-pathology was detected with FDG-PET.     

Multi-Parametric MRI and Texture Analysis to Visualize Spatial Histologic Heterogeneity and Tumor Extent in Glioblastoma

Background

Genetic profiling represents the future of neuro-oncology but suffers from inadequate biopsies in heterogeneous tumors like Glioblastoma (GBM). Contrast-enhanced MRI (CE-MRI) targets enhancing core (ENH) but yields adequate tumor in only ~60% of cases. Further, CE-MRI poorly localizes infiltrative tumor within surrounding non-enhancing parenchyma, or brain-around-tumor (BAT), despite the importance of characterizing this tumor segment, which universally recurs. In this study, we use multiple texture analysis and machine learning (ML) algorithms to analyze multi-parametric MRI, and produce new images indicating tumor-rich targets in GBM.

Methods

We recruited primary GBM patients undergoing image-guided biopsies and acquired pre-operative MRI: CE-MRI, Dynamic-Susceptibility-weighted-Contrast-enhanced-MRI, and Diffusion Tensor Imaging. Following image coregistration and region of interest placement at biopsy locations, we compared MRI metrics and regional texture with histologic diagnoses of high- vs low-tumor content (≥80% vs <80% tumor nuclei) for corresponding samples. In a training set, we used three texture analysis algorithms and three ML methods to identify MRI-texture features that optimized model accuracy to distinguish tumor content. We confirmed model accuracy in a separate validation set.

Results

We collected 82 biopsies from 18 GBMs throughout ENH and BAT. The MRI-based model achieved 85% cross-validated accuracy to diagnose high- vs low-tumor in the training set (60 biopsies, 11 patients). The model achieved 81.8% accuracy in the validation set (22 biopsies, 7 patients).

Conclusion

Multi-parametric MRI and texture analysis can help characterize and visualize GBM’s spatial histologic heterogeneity to identify regional tumor-rich biopsy targets.     

A Randomized Study of the Effects of Additional Fruit and Nuts Consumption on Hepatic Fat Content,Cardiovascular Risk Factors and Basal Metabolic Rate

Background

Fruit has since long been advocated as a healthy source of many nutrients, however, the high content of sugars in fruit might be a concern.

Objectives

To study effects of an increased fruit intake compared with similar amount of extra calories from nuts in humans.

Methods

Thirty healthy non-obese participants were randomized to either supplement the diet with fruits or nuts, each at +7 kcal/kg bodyweight/day for two months. Major endpoints were change of hepatic fat content (HFC, by magnetic resonance imaging, MRI), basal metabolic rate (BMR, with indirect calorimetry) and cardiovascular risk markers.

Results

Weight gain was numerically similar in both groups although only statistically significant in the group randomized to nuts (fruit: from 22.15±1.61 kg/m² to 22.30±1.7 kg/m², p = 0.24 nuts: from 22.54±2.26 kg/m² to 22.73±2.28 kg/m², p = 0.045). On the other hand BMR increased in the nut group only (p = 0.028). Only the nut group reported a net increase of calories (from 2519±721 kcal/day to 2763±595 kcal/day, p = 0.035) according to 3-day food registrations. Despite an almost three-fold reported increased fructose-intake in the fruit group (from 9.1±6.0 gram/day to 25.6±9.6 gram/day, p<0.0001, nuts: from 12.4±5.7 gram/day to 6.5±5.3 gram/day, p = 0.007) there was no change of HFC. The numerical increase in fasting insulin was statistical significant only in the fruit group (from 7.73±3.1 pmol/l to 8.81±2.9 pmol/l, p = 0.018, nuts: from 7.29±2.9 pmol/l to 8.62±3.0 pmol/l, p = 0.14). Levels of vitamin C increased in both groups while α-tocopherol/cholesterol-ratio increased only in the fruit group.

Conclusions

Although BMR increased in the nut-group only this was not linked with differences in weight gain between groups which potentially could be explained by the lack of reported net caloric increase in the fruit group. In healthy non-obese individuals an increased fruit intake seems safe from cardiovascular risk perspective, including measurement of HFC by MRI.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02227511","term_id":"NCT02227511"}}NCT02227511     

Diffusion Tensor Magnetic Resonance Imaging of Trigeminal Nerves in Relapsing Herpetic Keratouveitis

Background

Corneal hypoesthesia is the landmark of HSV and VZV keratitis and can lead to neurotrophic keratitis. Diffusion tensor imaging (DTI) is a new magnetic resonance imaging (MRI) derived technique, which offers possibilities to study axonal architecture. We aimed at assessing the potential impact of recurrent HSV or VZV-related keratitis on the axonal architecture of trigeminal nerves using DTI.

Design

Prospective non-interventional study.

Participants

Twelve patients and 24 controls.

Methods

DTI using MRI of the trigeminal fibers and corneal esthesiometry using the Cochet-Bonnet esthesiometer were acquired for patients affected by unilateral and recurrent HSV or VZV-related keratitis (3 months after the last corneal inflammatory event), and control subjects with no history of ocular or neuronal disease affecting the trigeminal pathways.

Main Outcome Measures

Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were compared between the 2 eyes of both patients and controls, and correlated with corneal esthesiometry.

Results

FA was lower in the trigeminal fibers ipsilateral to the affected eye compared to the non-affected side (0.39±0.02 versus 0.46±0.04, P=0.03). This difference was more important than the intra-individual variability observed in controls. Concomitantly, the asymmetry in ADC results was significantly correlated with the loss of corneal sensitivity in the affected eye.

Conclusions

Corneal hypoesthesia related to HSV and VZV keratitis is associated with persistent modifications in the architecture and functionality of the trigeminal fibers. These results add further explanation to the pathogenesis of HSV and VZV-induced neurotrophic keratitis, which may occur despite an apparent quiescence of the disease.     

Tracking Parkinson’s Disease over One Year with Multimodal Magnetic Resonance Imaging in a Group of Older Patients with Moderate Disease

Background & Objectives

Cross-sectional magnetic resonance imaging (MRI) suggests that Parkinson’s disease (PD) is associated with changes in cerebral tissue volume, diffusion tensor imaging metrics, and perfusion values. Here, we performed a longitudinal multimodal MRI study—including structural, diffusion tensor imaging (DTI), and perfusion MRI—to investigate progressive brain changes over one year in a group of older PD patients at a moderate stage of disease.

Methods

Twenty-three non-demented PD (mean age (SD) = 69.5 (6.4) years, disease duration (SD) = 5.6 (4.3) years) and 23 matched control participants (mean age: 70.6 (6.8)) completed extensive neuropsychological and clinical assessment, and multimodal 3T MRI scanning at baseline and one year later. We used a voxel-based approach to assess change over time and group-by-time interactions for cerebral structural and perfusion metrics.

Results

Compared to controls, in PD participants there was localized grey matter atrophy over time in bilateral inferior and right middle temporal, and left orbito-frontal cortices. Using a voxel-based approach that focused on the centers of principal white matter tracts, the PD and control cohorts exhibited similar levels of change in DTI metrics. There was no significant change in perfusion, cognitive, or motor severity measures.

Conclusions

In a cohort of older, non-demented PD participants, macrostructural MRI detected atrophy in the PD group compared with the control group in temporal and orbito-frontal cortices. Changes in diffusion MRI along principal white matter tracts over one year were found, but this was not differentially affected by PD.     

Predicting Prostate Biopsy Outcomes: A Preliminary Investigation on Screening with Ultrahigh B-Value Diffusion-Weighted Imaging as an Innovative Diagnostic Biomarker

Background

Routine screening of prostate specific antigen (PSA) is no longer recommended because of a high rate of over-diagnosis of prostate cancer (PCa).

Objective

To evaluate the efficacy of diffusion-weighted magnetic resonance imaging (DW-MRI) for PCa detection, and to explore the clinical utility of ultrahigh b-value DW-MRI in predicting prostate biopsy outcomes.

Methodology

73 male patients were selected for the study. They underwent 3T MRI using T2WI conventional DW-MRI with b-value 1000 s/mm², and ultrahigh b-value DW-MRI with b-values of 2000 s/mm² and 3000 s/mm². Two radiologists evaluated individual prostate gland images on a 5-point rating scale using PI-RADS, for the purpose of region-specific comparisons among modalities. Sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV) and likelihood ratios (LR) were investigated for each MRI modality. The area under the receiver operating characteristic (ROC) curve (AUC) was also calculated.

Results

Results showed the improved diagnostic value of ultrahigh b-value DWI-MRI for detection of PCa when compared to other b values and conventional MRI protocols. Sensitivity values for 3000 s/mm² in both peripheral zone (PZ) and transition zone (TZ) were significantly higher than those observed with conventional DW-MRI—Specificity values for 3000 s/mm² in the TZ were significantly higher than other b-value images, whereas specificity values using 3000 s/mm² in the PZ were not significantly higher than 2000 s/mm² images. PPV and NPV between 3000 s/mm² and the other three modalities were significantly higher for both PZ and TZ images. The PLRs and NLRs of b-value 3000 s/mm² DW-MRI in the PZ and TZ were also recorded. ROC analysis showed greater AUCs for the b value 3000 s/mm² DWI than for the other three modalities.

Conclusions

DW-MRI with a b-value of 3000 s/mm² was found to be the most accurate and reliable MRI modality for PCa tumor detection and localization, particularly for TZ lesion discrimination. It may be stated that the b-value of 3000 s/mm² is a novel, improved diagnostic biomarker with greater predictive accuracy for PCa prior to biopsy.     

Efficacy of a Community-Based Physical Activity Program KM2H2 for Stroke and Heart Attack Prevention among Senior Hypertensive Patients: A Cluster Randomized Controlled Phase-II Trial

Objective

To evaluate the efficacy of the program Keep Moving toward Healthy Heart and Healthy Brain (KM2H²) in encouraging physical activities for the prevention of heart attack and stroke among hypertensive patients enrolled in the Community-Based Hypertension Control Program (CBHCP).

Design

Cluster randomized controlled trial with three waves of longitudinal assessments at baseline, 3 and 6 months post intervention.

Setting

Community-based and patient-centered self-care for behavioral intervention in urban settings of China.

Participants

A total of 450 participants diagnosed with hypertension from 12 community health centers in Wuhan, China were recruited, and were randomly assigned by center to receive either KM2H² plus standard CBHCP care (6 centers and 232 patients) or the standard care only (6 centers and 218 patients).

Intervention

KM2H² is a behavioral intervention guided by the Transtheoretical Model, the Model of Personalized Medicine and Social Capital Theory. It consists of six intervention sessions and two booster sessions engineered in a progressive manner. The purpose is to motivate and maintain physical activities for the prevention of heart attack and stroke.

Outcome Measures

Heart attack and stroke (clinically diagnosed, primary outcome), blood pressure (measured, secondary outcome), and physical activity (self-report, tertiary outcome) were assessed at the individual level during the baseline, 3- and 6-month post-intervention.

Results

Relative to the standard care, receiving KM2H² was associated with significant reductions in the incidence of heart attack (3.60% vs. 7.03%, p < .05) and stroke (5.11% vs. 9.90%, p<0.05), and moderate reduction in blood pressure (-3.72mmHg in DBP and -2.92 mmHg in DBP) at 6-month post-intervention; and significant increases in physical activity at 3- (d = 0.53, 95% CI: 0.21, 0.85) and 6-month (d = 0.45, 95% CI: 0.04, 0.85) post-intervention, respectively.

Conclusion

The program KM2H² is efficacious to reduce the risk of heart attack and stroke among senior patients who are on anti-hypertensive medication. Findings of this study provide solid data supporting a formal phase-III trial to establish the effectiveness of KM2H² for use in community settings for prevention.

Trial Registration

ISRCTN Register ISRCTN12608966     

Clinical Implications of Diffuse Excessive High Signal Intensity (DEHSI) on Neonatal MRI in School Age Children Born Extremely Preterm

Objective

Magnetic resonance imaging (MRI) of the brain carried out during the neonatal period shows that 55–80% of extremely preterm infants display white matter diffuse excessive high signal intensity (DEHSI). Our aim was to study differences in developmental outcome at the age of 6.5 years in children born extremely preterm with and without DEHSI.

Study Design

This was a prospective cohort study of 83 children who were born in Stockholm, Sweden, between 2004 and 2007, born at gestational age of < 27 weeks + 0 days and who underwent an MRI scan of their brain at term equivalent age. The outcome measures at 6.5 years included testing 66 children with the modified Touwen neurology examination, the Movement Assessment Battery for Children 2, the Wechsler Intelligence Scale for Children—Fourth Edition, Beery Visual-motor Integration test—Sixth Edition, and the Strengths and Difficulties Questionnaire. Group-wise comparisons were done between children with and without DEHSI using Student t-test, Mann Whitney U test, Chi square test and regression analysis.

Results

DEHSI was detected in 39 (59%) of the 66 children who were assessed at 6.5 years. The presence of DEHSI was not associated with mild neurological dysfunction, scores on M-ABC assessment, cognition, visual-motor integration, or behavior at 6.5 years.

Conclusion

The presence of qualitatively defined DEHSI on neonatal MRI did not prove to be a useful predictor of long-term impairment in children born extremely preterm.     

Hyperthermic Laser Ablation of Recurrent Glioblastoma Leads to Temporary Disruption of the Peritumoral Blood Brain Barrier

Background

Poor central nervous system penetration of cytotoxic drugs due to the blood brain barrier (BBB) is a major limiting factor in the treatment of brain tumors. Most recurrent glioblastomas (GBM) occur within the peritumoral region. In this study, we describe a hyperthemic method to induce temporary disruption of the peritumoral BBB that can potentially be used to enhance drug delivery.

Methods

Twenty patients with probable recurrent GBM were enrolled in this study. Fourteen patients were evaluable. MRI-guided laser interstitial thermal therapy was applied to achieve both tumor cytoreduction and disruption of the peritumoral BBB. To determine the degree and timing of peritumoral BBB disruption, dynamic contrast-enhancement brain MRI was used to calculate the vascular transfer constant (K^trans) in the peritumoral region as direct measures of BBB permeability before and after laser ablation. Serum levels of brain-specific enolase, also known as neuron-specific enolase, were also measured and used as an independent quantification of BBB disruption.

Results

In all 14 evaluable patients, K^trans levels peaked immediately post laser ablation, followed by a gradual decline over the following 4 weeks. Serum BSE concentrations increased shortly after laser ablation and peaked in 1–3 weeks before decreasing to baseline by 6 weeks.

Conclusions

The data from our pilot research support that disruption of the peritumoral BBB was induced by hyperthemia with the peak of high permeability occurring within 1–2 weeks after laser ablation and resolving by 4–6 weeks. This provides a therapeutic window of opportunity during which delivery of BBB-impermeant therapeutic agents may be enhanced.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01851733","term_id":"NCT01851733"}}NCT01851733     

Predicting Risk of Motor Vehicle Collisions in Patients with Glaucoma: A Longitudinal Study

Purpose

To evaluate the ability of longitudinal Useful Field of View (UFOV) and simulated driving measurements to predict future occurrence of motor vehicle collision (MVC) in drivers with glaucoma.

Design

Prospective observational cohort study.

Participants

117 drivers with glaucoma followed for an average of 2.1 ± 0.5 years.

Methods

All subjects had standard automated perimetry (SAP), UFOV, driving simulator, and cognitive assessment obtained at baseline and every 6 months during follow-up. The driving simulator evaluated reaction times to high and low contrast peripheral divided attention stimuli presented while negotiating a winding country road, with central driving task performance assessed as “curve coherence”. Drivers with MVC during follow-up were identified from Department of Motor Vehicle records.

Main Outcome Measures

Survival models were used to evaluate the ability of driving simulator and UFOV to predict MVC over time, adjusting for potential confounding factors.

Results

Mean age at baseline was 64.5 ± 12.6 years. 11 of 117 (9.4%) drivers had a MVC during follow-up. In the multivariable models, low contrast reaction time was significantly predictive of MVC, with a hazard ratio (HR) of 2.19 per 1 SD slower reaction time (95% CI, 1.30 to 3.69; P = 0.003). UFOV divided attention was also significantly predictive of MVC with a HR of 1.98 per 1 SD worse (95% CI, 1.10 to 3.57; P = 0.022). Global SAP visual field indices in the better or worse eye were not predictive of MVC. The longitudinal model including driving simulator performance was a better predictor of MVC compared to UFOV (R² = 0.41 vs R² = 0.18).

Conclusions

Longitudinal divided attention metrics on the UFOV test and during simulated driving were significantly predictive of risk of MVC in glaucoma patients. These findings may help improve the understanding of factors associated with driving impairment related to glaucoma.     

In Vivo Tumor Growth Rate Measured by US in Preoperative Period and Long Term Disease Outcome in Breast Cancer Patients

Objective

The aim of our study was to evaluate the effect of tumor growth rate, calculated from tumor size measurements by US, on breast cancer patients’ outcome.

Patients and Methods

Breast cancer patients who received at least two serial breast ultrasonographies (US) in our institution during preoperative period and were surgically treated between 2002 and 2010 were reviewed. Tumor growth rate was determined by specific growth rate (SGR) using the two time point tumor sizes by US.

Results

A total of 957 patients were analyzed. The median duration between initial and second US was 28 days (range, 8–140). The median initial tumor size was 1.7cm (range, 0.4–7.0) and median second size was 1.9cm (range, 0.3–7.2). 523(54.6%) cases had increase in size. The median SGR(x10^-2) was 0.59 (range, -11.90~31.49) and mean tumor doubling time was 14.51 days. Tumor growth rate was higher when initial tumor size was smaller. Lymphovascular invasion, axillary lymph node metastasis, and higher histologic grade were significantly associated with higher SGR. SGR was significantly associated with disease-free survival (DFS) in a univariate analysis (p = 0.04), but not in a multivariate Cox analysis (p>0.05). High SGR was significantly associated with worse DFS in a subgroup of initial tumor size >2cm (p = 0.018), but not in those with tumor size <2cm (p>0.05).

Conclusion

Our results showed that tumor growth rate measured by US in a relatively short time interval was associated with other worse prognostic factors and DFS, but it was not an independent prognostic factor in breast cancer patients.     

Diffusion-Weighted Imaging in 3.0 Tesla Breast MRI: Diagnostic Performance and Tumor Characterization Using Small Subregions vs. Whole Tumor Regions of Interest

Introduction

Apparent diffusion coefficient (ADC) values are increasingly reported in breast MRI. As there is no standardized method for ADC measurements, we evaluated the effect of the size of region of interest (ROI) to diagnostic utility and correlation to prognostic markers of breast cancer.

Methods

This prospective study was approved by the Institutional Ethics Board; the need for written informed consent for the retrospective analyses of the breast MRIs was waived by the Chair of the Hospital District. We compared diagnostic accuracy of ADC measurements from whole-lesion ROIs (WL-ROIs) to small subregions (S-ROIs) showing the most restricted diffusion and evaluated correlations with prognostic factors in 112 consecutive patients (mean age 56.2±11.6 years, 137 lesions) who underwent 3.0-T breast MRI.

Results

Intra- and interobserver reproducibility were substantial (κ = 0.616–0.784; Intra-Class Correlation 0.589–0.831). In receiver operating characteristics analysis, differentiation between malignant and benign lesions was excellent (area under curve 0.957–0.962, cut-off ADC values for WL-ROIs: 0.87×10⁻³ mm²s^-1; S-ROIs: 0.69×10⁻³ mm²s^-1, P<0.001). WL-ROIs/S-ROIs achieved sensitivities of 95.7%/91.3%, specificities of 89.5%/94.7%, and overall accuracies of 89.8%/94.2%. In S-ROIs, lower ADC values correlated with presence of axillary metastases (P = 0.03), high histological grade (P = 0.006), and worsened Nottingham Prognostic Index Score (P<0.05). In both ROIs, ADC values correlated with progesterone receptors and advanced stage (P<0.01), but not with HER2, estrogen receptors, or Ki-67.

Conclusions

ADC values assist in breast tumor characterization. Small ROIs were more accurate than whole-lesion ROIs and more frequently associated with prognostic factors. Cut-off values differed significantly depending on measurement procedure, which should be recognized when comparing results from the literature. Instead of using a whole lesion covering ROI, a small ROI could be advocated in diffusion-weighted imaging.     

Multimodal Imaging of Orthotopic Mouse Model of Endometrial Carcinoma

Background

Orthotopic endometrial cancer models provide a unique tool for studies of tumour growth and metastatic spread. Novel preclinical imaging methods also have the potential to quantify functional tumour characteristics in vivo, with potential relevance for monitoring response to therapy.

Methods

After orthotopic injection with luc-expressing endometrial cancer cells, eleven mice developed disease detected by weekly bioluminescence imaging (BLI). In parallel the same mice underwent positron emission tomography–computed tomography (PET-CT) and magnetic resonance imaging (MRI) employing ¹⁸F-fluorodeoxyglocose (¹⁸F-FDG) or ¹⁸F- fluorothymidine (¹⁸F-FLT) and contrast reagent, respectively. The mice were sacrificed when moribund, and post-mortem examination included macroscopic and microscopic examination for validation of growth of primary uterine tumours and metastases. PET-CT was also performed on a patient derived model (PDX) generated from a patient with grade 3 endometrioid endometrial cancer.

Results

Increased BLI signal during tumour growth was accompanied by increasing metabolic tumour volume (MTV) and increasing MTV x mean standard uptake value of the tumour (SUV_mean) in ¹⁸F-FDG and ¹⁸F-FLT PET-CT, and MRI conspicuously depicted the uterine tumour. At necropsy 82% (9/11) of the mice developed metastases detected by the applied imaging methods. ¹⁸F-FDG PET proved to be a good imaging method for detection of patient derived tumour tissue.

Conclusions

We demonstrate that all imaging modalities enable monitoring of tumour growth and metastatic spread in an orthotopic mouse model of endometrial carcinoma. Both PET tracers, ¹⁸F-FDG and ¹⁸F-FLT, appear to be equally feasible for detecting tumour development and represent, together with MRI, promising imaging tools for monitoring of patient-derived xenograft (PDX) cancer models.     

Nurse-Led Medicines' Monitoring for Patients with Dementia in Care Homes: A Pragmatic Cohort Stepped Wedge Cluster Randomised Trial

Background

People with dementia are susceptible to adverse drug reactions (ADRs). However, they are not always closely monitored for potential problems relating to their medicines: structured nurse-led ADR Profiles have the potential to address this care gap. We aimed to assess the number and nature of clinical problems identified and addressed and changes in prescribing following introduction of nurse-led medicines’ monitoring.

Design

Pragmatic cohort stepped-wedge cluster Randomised Controlled Trial (RCT) of structured nurse-led medicines’ monitoring versus usual care.

Setting

Five UK private sector care homes

Participants

41 service users, taking at least one antipsychotic, antidepressant or anti-epileptic medicine.

Intervention

Nurses completed the West Wales ADR (WWADR) Profile for Mental Health Medicines with each participant according to trial step.

Outcomes

Problems addressed and changes in medicines prescribed.

Data Collection and Analysis

Information was collected from participants’ notes before randomisation and after each of five monthly trial steps. The impact of the Profile on problems found, actions taken and reduction in mental health medicines was explored in multivariate analyses, accounting for data collection step and site.

Results

Five of 10 sites and 43 of 49 service users approached participated. Profile administration increased the number of problems addressed from a mean of 6.02 [SD 2.92] to 9.86 [4.48], effect size 3.84, 95% CI 2.57–4.11, P <0.001. For example, pain was more likely to be treated (adjusted Odds Ratio [aOR] 3.84, 1.78–8.30), and more patients attended dentists and opticians (aOR 52.76 [11.80–235.90] and 5.12 [1.45–18.03] respectively). Profile use was associated with reduction in mental health medicines (aOR 4.45, 1.15–17.22).

Conclusion

The WWADR Profile for Mental Health Medicines can improve the quality and safety of care, and warrants further investigation as a strategy to mitigate the known adverse effects of prescribed medicines.

Trial Registration

ISRCTN 48133332     

Direct Healthcare Cost of Obesity in Brazil: An Application of the Cost-of-Illness Method from the Perspective of the Public Health System in 2011

Background

Obesity is a global public health problem and a risk factor for several diseases that financially impact healthcare systems.

Objective

To estimate the direct costs attributable to obesity (body mass index {BMI} ≥ 30 kg/m²) and morbid obesity (BMI ≥ 40 kg/m²) in adults aged ≥ 20 incurred by the Brazilian public health system in 2011.

Settings

Public hospitals and outpatient care.

Methods

A cost-of-illness method was adopted using a top-down approach based on prevalence. The proportion of the cost of each obesity-associated comorbidity was calculated and obesity prevalence was used to calculate attributable risk. Direct healthcare cost data (inpatient care, bariatric surgery, outpatient care, medications and diagnostic procedures) were extracted from the Ministry of Health information systems, available on the web.

Results

Direct costs attributable to obesity totaled US$ 269.6 million (1.86% of all expenditures on medium- and high-complexity health care). The cost of morbid obesity accounted for 23.8% (US$ 64.2 million) of all obesity-related costs despite being 18 times less prevalent than obesity. Bariatric surgery costs in Brazil totaled US$ 17.4 million in 2011. The cost of morbid obesity in women was five times higher than it was in men.

Conclusion

The cost of morbid obesity was found to be proportionally higher than the cost of obesity. If the current epidemic were not reversed, the prevalence of obesity in Brazil will increase gradually in the coming years, as well as its costs, having serious implications for the financial sustainability of the Brazilian public health system.     

Accuracy of [18F]FDG PET/MRI for the Detection of Liver Metastases

Background

The aim of this study was to compare the diagnostic accuracy of [¹⁸F]FDG-PET/MRI with PET/CT for the detection of liver metastases.

Methods

32 patients with solid malignancies underwent [¹⁸F]FDG-PET/CT and subsequent PET/MRI of the liver. Two readers assessed both datasets regarding lesion characterization (benign, indeterminate, malignant), conspicuity and diagnostic confidence. An imaging follow-up (mean interval: 185±92 days) and/-or histopathological specimen served as standards of reference. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for both modalities. Accuracy was determined by calculating the area under the receiver operating characteristic (ROC) curve. Values of conspicuity and diagnostic confidence were compared using Wilcoxon-signed-rank test.

Results

The standard of reference revealed 113 liver lesions in 26 patients (malignant: n = 45; benign: n = 68). For PET/MRI a higher accuracy (PET/CT: 82.4%; PET/MRI: 96.1%; p<0.001) as well as sensitivity (67.8% vs. 92.2%, p<0.01) and NPV (82.0% vs. 95.1%, p<0.05) were observed. PET/MRI offered higher lesion conspicuity (PET/CT: 2.0±1.1 [median: 2; range 0–3]; PET/MRI: 2.8±0.5 [median: 3; range 0–3]; p<0.001) and diagnostic confidence (PET/CT: 2.0±0.8 [median: 2; range: 1–3]; PET/MRI 2.6±0.6 [median: 3; range: 1–3]; p<0.001). Furthermore, PET/MRI enabled the detection of additional PET-negative metastases (reader 1: 10; reader 2: 12).

Conclusions

PET/MRI offers higher diagnostic accuracy compared to PET/CT for the detection of liver metastases.