Signal-to-noise ratio of diffusion weighted magnetic resonance imaging: Estimation methods and in vivo application to spinal cord

Diffusion tensor imaging (DTI) and tractographic reconstruction may be applied for in vivo clinical spinal cord studies. However, this structure represents a challenge to current acquisition and reconstruction strategies, due to its small size, motion artifacts, partial volume effects and low signal-to-noise-ratio (SNR). Aims of this work were to select the best approach for the estimate of SNR and to use it for spinal cord diffusion weighted (DW) sequence optimization.Seven methods for the estimate of SNR were compared on uniform phantom DW images, and the best performing approach (single ROI for signal and noise, difference of images—SNR_diff) was applied for the following in vivo sequence evaluations.Fifteen sequences with different parameters (voxel size, repetition (TR) and echo (TE) times) were compared according to SNR, resolution, fractional anisotropy (FA) and tractography performances on three healthy volunteers. In vivo optimization of DW sequences resulted in: axial sequence, with voxel size = 1.5 mm × 1.5 mm × 3.5 mm, TR = 3200 ms and TE = 89 ms, sagittal sequence with voxel size = 2.2 mm × 2.2 mm × 2 mm, TR = 3000 ms and TE = 84 ms.An objective method tested on phantom and a practical index for in vivo spinal cord DTI SNR estimation allowed to obtain axial and sagittal optimized sequences, providing excellent tractographic results, with acceptable acquisition times for in vivo clinical applications.     

Comparaison IRM de diffusion corps entier et TEP/TDM au 18FDG dans le diagnostic de myélome symptomatique

IntroductionOur work aims to compare whole-body diffusion MRI (DWMRI) and ¹⁸FDG PET/CT in the diagnosis of symptomatic myeloma.Patients and methodFrom November 2008 till May 2010, 19 patients were investigated by DWMRI and by ¹⁸FDG PET/CT. The patients were classified according to the criteria of the International Myeloma Working Group in eight non-symptomatic myelomas and 11 symptomatic myelomas. The sensitivity and the specificity of two methods of imaging were studied by retaining the presence or the absence of a diffuse infiltration (ID), focal lesions (FL), or both parameters (FL + ID), in both modalities of imaging. We compared the concordance between two techniques for every patient by using these signs using a weighted kappa test.ResultsThe performances of both modalities seem comparable, with superior diagnostic performances for the FL (Se = 100% and Sp = 75% in DWMRI and Se = 91% and Sp = 75% for ¹⁸FDG PET/CT). By combining both parameters, the ¹⁸FDG PET/CT seems more specific, but the sensitivity is comparable in both modalities (Se = 100% in MRI and Se = 100% in ¹⁸FDG PET/CT; Sp = 37% in DWMRI and Sp = 62% for ¹⁸FDG PET/CT). The concordance between both techniques is better by taking into account the FL than the other parameters (weighted kappa = 0.61 for FL, 0.5 for the FL + ID and 0.16 for ID alone).ConclusionDiagnostic performances of whole-body diffusion MRI and ¹⁸FDG PET/CT seem equivalent, but concordance between both techniques is imperfect. Further studies are necessary to understand this discrepancy.     

Segmentation d’images de lésions cérébrales primitives en TEP FET : influence du volume de travail

Purpose(1) Evaluate the reproducibility of segmentation methods depending on the preselection region for tumour volume determination on ¹⁸F-fluoro-ethyl-tyrosine (FET) PET. (2) Evaluate the intra and inter-operator reproducibility of the manual delineation. (3) Compare this delineation with the segmentation methods.Materials and methodsEighteen FET PET of patients with glioblastoma were analysed. Preselection regions were determined prior to any segmentation. Two physicians delineated the tumour volume manually. The tumour volume was also delineated with a threshold method (40 and 70% of SUV_max), and a random walk based method. Pearson coefficient (r) (P < 0.05 for r > 0.468) and Jaccard indices (JI) were used to compare the volumes.ResultsManual delineation was reproducible with r = 0.97 and IJ = 0.65 for intra-operator, and r = 0.76 and IJ = 0.45 for inter-operator reproducibility. The preselection regions for a given lesion were different and the segmentation varied with the preselection region: r = 0.55 JI = 0.58; r = 0.85 JI = 0.83; r = 0.70 JI = 0.39 respectively for the threshold of 40%, 70% and the random walk. The segmentation differed form de manual delineation with r = 0.37 and JI = 0.16; r = 0.54 and JI = 0.42; r = 0.43 and JI = 0.37 respectively for the threshold of 40%, 70% and the random walk.ConclusionThe reproducibility of the segmentation methods depends extensively on the preselection region. The intra-operator reproducibility of cerebral lesion delineation on FET PET is satisfactory. The inter-operator reproducibility could be improved.     

Évaluation par la TEMP–TDM des lésions classées indéterminées en scintigraphie osseuse chez les patients de cancérologie

The aim of the present study was to investigate the contribution of the single photon emission computed tomography/computed tomography (SPECT/CT) in cancer patients and to evaluate its ability to correctly classify indeterminate lesions on planar bone scintigraphy (PBS).MethodsFrom November 2006 to August 2007, all patients with confirmed malignancy, whose PBS showed indeterminate lesions, underwent without delay a SPECT/CT. The study included 120 patients (67 men, 53 women), with a mean age of 69 ± 12 years (range 42–96 years). The patients with obvious metastases, important pains or who did not accept the examination were excluded from the study. The location of the lesions was described either as precise, probable or indeterminate. The lesions were classified either as definitely malignant, definitely benign or indeterminate.ResultsBreast, prostate, lung and kidney neoplasms represented approximately 80% of all cancers. The PBS highlighted 267 lesions of location either as precise (n = 29), probable (n = 129) or indeterminate (n = 109), classified either as definitely malignant (n = 28), definitely benign (n = 27) or indeterminate (n = 212). The SPECT/CT revealed 440 lesions, of location either as precise (n = 353), likely (n = 39) or indeterminate (n = 48), classified either as definitely malignant (n = 84), definitely benign (n = 305) or indeterminate (n = 51). Thoracic and lumbar spine and pelvis were the locations of 79% of the scintigraphic lesions and of 88% of the osseous metastases. SPECT/CT modified the final report of 80 patients, by excluding from metastases (n = 2), by showing metastases (n = 23) and by showing the benign character of indeterminate lesions (n = 55). Moreover, 69 patients out of 120 (> 57%) had an evolution confirmed with 35 true positives, 31 true negatives, one false negative and two patients with indeterminate lesions on SPECT/CT, without osseous metastasis.ConclusionThe assessment of the indeterminate scintigraphic lesions of oncologic patients benefits from the SPECT/CT. The lesion-based analysis showed that the SPECT/CT detected more lesions (+64%) and correctly classified 88% of the detected lesions. The patient-based analysis highlighted that SPECT/CT modified the final report for more than 66% of the patients. The follow-up showed that SPECT/CT correctly classified for more than 95% of the patients.     

Differential diagnosis between progression and radionecrosis in brain metastases after stereotactic radiosurgery using hybrid FDG-PET and MRI coregistered images

IntroductionDual phase 18 FDG brain PET is helpful to assess brain metastases (BM) as tracer will build up in metastases or tumor recurrences while its retention remains stable within normal tissue or inflammatory processes. This is useful when MRI can’t discriminate brain tumor recurrence (TR) rom radionecrosis (RN) after stereotaxic radiosurgery (SRS) for BM. Many studies have sought to improve diagnostic performance by associating FDG-PET and MRI with interesting results but many biases, mostly within image post-processing. Coregistered MRI and dual phase FDG-PET images could alleviate these biases and be used to extract prognostic biomarkers.Materials and methodsWe retrospectively evaluated patients treated with SRS for BM which developed a contrast-enhanced MRI lesion with non-conclusive diagnosis for TR or RN. All patients underwent MRI and FDG-PET at least 3 months after their last SRS session. Dual FDG-PET consisted in an “early” and “delayed” acquisition, respectively 30 minutes and 4 h after injection. MRI included permeability and perfusion sequences. PET and MRI data were all coregistered on the contrast enhanced T1 MRI images. Semi-automated Volumes of Interest (VOI) of the tumor were drawn on the BM and a reference contralateral white-matter ROI (WM) was drawn for standardization; every metric was calculated inside these ROIs, in particular the tumor SUVmax and its variation in time. A 20% increase in the tumor SUVmax was in favor of TR while a modification of less than 100% was in favor of RN. Imaging metrics were then evaluated for their association with TR or RN based on histological, radiological and clinical criteria after at least 6 months follow-up.ResultsNine patients were ruled out as TR and 6 as RN. After standardization, there was a significant difference between groups for VP (P = 0.042), Washin (P = 0.035), Peak Enhancement (P = 0.037), standardized delayed SUVmax (P = 0.008) and RI (P = 0.016). Semi-quantitative analysis found respectively for PET and MRI a Sensitivity of 100% and 87.5% and a Specificity of 100% and 85.71%.ConclusionCoregistered PET-MRI images accurately discriminate between TR and RN. With FDG being the most commonly used PET radiotracer, this protocol remains easily transposable and should be encouraged to obtain non-invasive prognostic and clinically relevant biomarkers.     

Novel formulation of a double threshold algorithm for the estimation of muscle activation intervals designed for variable SNR environments

The aim of this work is the development of an improved formulation of the double threshold algorithm for sEMG onset–offset detection presented by Bonato and co-workers. The original formulation, which keeps the threshold fixed, suffers from performance degradation whenever the SNR changes during the analysis. The novel approach is designed to be adaptive to SNR changes in either burst or inter-burst zones of sEMG signals recorded in static and dynamic conditions. The detection parameters (i.e. detection and false alarm probabilities) are updated on the basis of an on-line estimation of the SNR. The proposed formulation has been assessed on both simulated and real sEMG data. For constant SNR the performance of the original formulation is confirmed (for SNR > 8 dB, bias and standard deviation less than 10 and 15 ms, respectively; detection percentage higher than 95%), while the novel implementation performs better with time-varying SNR (for SNR varying in the range 10–25 dB the standard approach detection percentage decreases at 50%). Detection on signals recorded during isometric contractions at different force levels confirms the performance on simulated signals (StD = 134 ms; FP = 22%, and StD = 42 ms; FP = 2%, respectively for standard and novel implementation calculated as average on five experimental trials). The pseudo real-time detection allowed by this formulation can be profitably exploited by biofeedback applications based on myoelectric information.     

Temporal resolution measurement of 128-slice dual source and 320-row area detector computed tomography scanners in helical acquisition mode using the impulse method

PurposeTo analyse the temporal resolution (TR) of modern computed tomography (CT) scanners using the impulse method, and assess the actual maximum TR at respective helical acquisition modes.MethodsTo assess the actual TR of helical acquisition modes of a 128-slice dual source CT (DSCT) scanner and a 320-row area detector CT (ADCT) scanner, we assessed the TRs of various acquisition combinations of a pitch factor (P) and gantry rotation time (R).ResultsThe TR of the helical acquisition modes for the 128-slice DSCT scanner continuously improved with a shorter gantry rotation time and greater pitch factor. However, for the 320-row ADCT scanner, the TR with a pitch factor of <1.0 was almost equal to the gantry rotation time, whereas with pitch factor of >1.0, it was approximately one half of the gantry rotation time. The maximum TR values of single- and dual-source helical acquisition modes for the 128-slice DSCT scanner were 0.138 (R/P = 0.285/1.5) and 0.074 s (R/P = 0.285/3.2), and the maximum TR values of the 64 × 0.5- and 160 × 0.5-mm detector configurations of the helical acquisition modes for the 320-row ADCT scanner were 0.120 (R/P = 0.275/1.375) and 0.195 s (R/P = 0.3/0.6), respectively.ConclusionBecause the TR of a CT scanner is not accurately depicted in the specifications of the individual scanner, appropriate acquisition conditions should be determined based on the actual TR measurement.     

Tomographie sténopéïque au 99mTc-MIBI dans l’hyperparathyroïdie primaire

PurposeThis prospective study was conducted to determine the interest of ^99mTc-MIBI pinhole SPECT compared with conventional SPECT, planar scintigraphy and ultrasonography, for the preoperative localization of parathyroid lesions in primary hyperparathyroidism.MethodsFifty-one patients cured after surgery were studied. Pinhole SPECT was reconstructed with a dedicated OSEM algorithm. Scintigraphies were analyzed visually. A diagnostic confidence score (CS) was assigned to each procedure considering intensity and extrathyroidal location of suspected lesions and was defined as follows: 0 = negative, 1 = doubtful, 2 = moderately positive, 3 = positive.ResultsSurgery revealed 55 lesions. Sensitivity of ultrasonography, planar imaging, conventional SPECT and pinhole SPECT were respectively, 51, 76, 82 and 87%. Five glands were only detected by pinhole SPECT. Combination of ultrasonography, planar and pinhole SPECT showed the highest sensitivity (94.5%). The mean CS of the 55 pathologic glands was significantly higher with pinhole SPECT compared with planar imaging and conventional SPECT (p < 0.0001). Compared with planar imaging and conventional SPECT, pinhole SPECT increased CS for 42 and 53% of parathyroid lesions, respectively, and contributed to markedly reduce the number of uncertain results. Nevertheless, planar imaging and ultrasonography were useful to analyze thyroid morphology and to detect some ectopic glands.ConclusionThe use of pinhole SPECT increases sensitivity and CS of scintigraphy. Combination of ultrasonography, planar and pinhole SPECT appears the optimal preoperative imaging procedure in primary hyperparathyroidism.     

Expression of the Androgen Receptor,pAkt, and pPTEN in Breast Cancer and Their Potential in Prognostication

BACKGROUNDImportance of androgen receptor (AR) as an independent prognostic marker in Pakistani women with breast cancer (BCa) remains unexplored. Our aim was to identify the expression and potential prognostic value of AR, its upstream regulator (pAkt) and target gene (pPTEN) in invasive BCa.METHODSThis study used a cohort of 200 Pakistani women with invasive BCa diagnosed during 2002-2011. Expression of AR, pAkt and pPTEN was determined on formalin fixed paraffin embedded tissue sections by immunohistochemistry. The association of AR, pAkt and pPTEN with clinicopathological parameters was determined. Survival analyses were undertaken on patients with ≥ 5 years of follow-up (n = 82).RESULTSExpression of AR, pAkt and pPTEN was observed in 47.5%, 81.3% and 50.6% of patients, respectively. AR-expressing tumors were low or intermediate in grade (P < .001) and expressed ER (P = .002) and PR (P = .001). Patients with AR⁺ tumors had significantly higher OS (Mean OS = 10.2 ± 0.465 years) compared to patients with AR^? tumors (Mean OS = 5.8 ± 0.348 years) (P = .047). Furthermore, AR-positivity was associated with improved OS in patients receiving endocrine therapy (P = .020). Patients with AR⁺ /pAkt⁺ /pPTEN^? tumors, had increased OS (Mean OS = 7.1 ± 0.535 years) compared to patients with AR^?/pAkt⁺/pPTEN^? tumors (Mean OS = 5.1 ± 0.738 years).CONCLUSIONAR-expressing tumors are frequently characterized by low or intermediate grade tumors, expressing ER and PR. In addition, expression of AR, pAkt and pPTEN, could be considered in prognostication of patients with invasive BCa.     

Immune mobilization of autologous blood progenitor cells: direct influence on the cellular subsets collected

Background aimsA phase I trial examined the ability of immunotherapy to mobilize progenitor and activated T cells.MethodsInterleukin (IL)-2 was administered subcutaneously for 11 days, with granulocyte (G)-colony-stimulating factor (CSF) (5 mcg/kg/day) and granulocyte–macrophage (GM)-CSF (7.5 mcg/kg/day) added for the last 5 days. Leukapheresis was initiated on day 11. Thirteen patients were treated (myeloma n = 11, non-Hodgkin's lymphoma n = 2).ResultsToxicities were minimal. IL-2 was stopped in two patients because of capillary leak (n = 1) and diarrhea (n = 1). Each patient required 2.5 leukaphereses (median; range 1–3) to collect 3.2 × 10⁶ CD34⁺ cells/kg (median; range 1.9–6.6 × 10⁶/kg). Immune mobilization increased the number of CD3⁺ CD8⁺ T cells (P = 0.002), CD56⁺ natural killer (NK) cells (P = 0.0001), CD8⁺ CD56⁺ T cells (P = 0.002) and CD4⁺ CD25⁺ cells (P = 0.0001) compared with cancer patients mobilized with G-CSF alone. There was increased lysis of myeloma cells after 7 days (P = 0.03) or 11 days (P = 0.02). The maximum tolerated dose of IL-2 was 1 × 10⁶ IU/m²/day.ConclusionsImmune mobilization is well tolerated with normal subsequent marrow engraftment. As cells within the graft influence lymphocyte recovery, an increased number of functional lymphocytes may result in more rapid immune reconstitution.     

La TEP au 18F-FDG dans le diagnostic et le suivi évolutif des plasmocytomes solitaires

AimTo assess the role of [¹⁸F]FDG-PET in solitary plasmacytoma with regards to staging, therapeutic follow-up and monitoring.Patients and methodsTwenty consecutive patients were included in the present study when following conditions were met: (i) solitary plasmacytoma histologically confirmed (bone, n = 16; extramedullary, n = 4); (ii) [¹⁸F]FDG-PET scan from July 2004 to April 2009. The clinical follow-up was over than 2 years for 13 patients. Ten patients underwent a post-therapy PET scan. PET scans were visually analysed.ResultsPET scan enabled confirmation of all main lesions (sensitivity: 100%) and also detected infra-clinical lesions in eight cases. Follow-up for more than 2 years showed a progression disease into myeloma in five from six cases (83%) with infraclinical lesions at the baseline PET scan. Among 10 patients who underwent post-therapeutic PET scan, six experienced a complete response at the main lesion site and four experienced a partial response.ConclusionFDG-PET may play an important role in plasmacytoma staging and enables detection of smaller lesions (otherwise undetected).     

Surveillance of effects of HPV vaccination in Belgium

BackgroundEarly effects of HPV (human papillomavirus) vaccination are reflected by changes observable in young women attending cervical cancer screening.Subject and methodsThe SEHIB study included HPV geno-typing of ∼6000 continuous and 650 pathological cervical cell specimen as well as biopsies, collected from women in Belgium in 2010–2014. Data were linked to vaccination status.ResultsHPV vaccination offered protection among women aged <30 years against infection with HPV16 (vaccine effectiveness [VE] = 67%, 95% CI: 48–79%), HPV18 (VE = 93%, 95% CI: 52–99%), and high-risk HPV (VE = 16%, 95% CI: 2–29%). Vaccination protected also against cytological lesions. Vaccination protected against histologically confirmed lesions: significantly lower absolute risks of CIN1+ (risk difference [RD] = −1.6%, 95% CI: −2.6% to −0.7%) and CIN3+ associated with HPV16/18 (RD = −0.3%, 95% CI −0.6% to −0.1%). Vaccine effectiveness decreased with age. Protection against HPV16 and 18 infection was significant in all age groups, however no protection was observed against cytological lesions associated with these types in age-group 25–29.ConclusionThe SEHIB study demonstrates the effectiveness of HPV vaccination in Belgian young women in particular in age group 18–19. Declining effectiveness with increasing age may be explained by higher tendency of women already exposed to infection to get the vaccine.     

Heart rate and arterial pressure variability and baroreflex sensitivity in ovariectomized spontaneously hypertensive rats

AimsThe present study evaluated the effects of ovariectomy on heart rate and arterial pressure variability and cardiac baroreflex sensitivity (BRS) in female spontaneously hypertensive (SHR) and Wistar–Kyoto rats (WKY).Main methodsSham-surgery animals were used as control. Sixteen weeks after ovariectomy or sham-surgery, animals were recorded. Time series of pulse interval (PI) and systolic AP (SAP) were analyzed by means of autoregressive spectral analysis, which quantifies the power of very low (VLF = 0.01–0.25 Hz), low (LF = 0.25–0.75 Hz) and high frequency (HF = 0.75–2.5 Hz) bands. BRS was assessed by means of linear regression between changes of PI and SAP induced by vasoactive drugs or calculation of α-index, a spontaneous BRS index.Key findingsThere was no difference in baseline PI or SAP between ovariectomized and sham SHR. Spectral analysis of heart rate variability suggested a shift of sympatho-vagal balance toward sympathetic predominance in ovariectomized SHR (LF/HF = 1.8 ± 0.2 versus 0.7 ± 0.2 in sham SHR, p < 0.05). Ovariectomy increased total variance and VLF power of SAP in SHR (29.1 ± 9.6 mmHg² and 18.6 ± 6.3 mmHg² versus 9.1 ± 2.1 mmHg² and 4.3 ± 1.4 mmHg², respectively, in sham SHR, p < 0.05). In addition, ovariectomy reduced reflex bradycardia in SHR (0.18 ± 0.03 ms/mmHg versus 0.34 ± 0.06 ms/mmHg in sham SHR, p < 0.05). Ovariectomy did not affect heart rate and SAP variability or BRS in WKY.SignificanceThese data showed that ovarian hormones deprivation induced marked changes on cardiovascular control, increasing SAP variability and cardiac sympatho-vagal balance and blunting BRS in female hypertensive animals, which reinforce the possible protective role of ovarian hormones on the cardiovascular system.     

Intérêt de la scintigraphie rénale au DMSA dans les pyélonéphrites aiguës de l’enfant

IntroductionAcute pyelonephritis is responsible for significant morbidity during the acute phase and distant irreversible kidney damage. However, diagnosis is often difficult in children. The aim of our study was to evaluate in children hospitalized for suspected acute pyelonephritis prevalence of acute lesions revealed by scintigraphy with ^99mTc labeled dimercaptosuccinic acid (DMSA) and the relationship between renal parenchymal lesions and different clinical factors and biological risks.MethodsThis is a prospective study collecting 40 children admitted with suspected infection of the high urinary tract. All have benefited from DMSA renal scintigraphy.ResultsThe average age of our patients was 3.25 years. The DMSA scan showed signs of acute pyelonephritis in 32.5% of cases. Taking this examination as a reference, fever was the most sensitive clinical signs (76.9%), but the specificity was only 48.1%. CRP (≥ 20 mg/mL) was the most sensitive (92.3%) but with a specificity of 40.7% organic signs. A high CRP was associated with acute pyelonephritis significantly (P = 0.0033). Sixty-three percent of refluxing kidneys were associated with acute pyelonephritis versus 20.8% of non-refluxing kidneys, with a significant difference (P = 0.007).ConclusionIn case of urinary tract infection in children, a complete clinical and laboratory table may be sufficient to retain the diagnosis of acute pyelonephritis. However, this possibility is rare. In the opposite case, a DMSA scan should be performed to confirm the diagnosis.     

Risk factors associated with human papillomavirus prevalence and cervical neoplasia among Cameroonian women

BackgroundThis study used community-based cervical cancer screening for high-risk human-papillomavirus (HPV) to determine demographic and lifestyle factors associated with HPV prevalence and cervical intraepithelial neoplasia grade 2 or worse (CIN2+).MethodsWomen (n = 838) aged 25–65 years were recruited in two sequential studies in Cameroon. Demographic and historical data were obtained from participants and specimens were self-collected for HPV-testing using real-time PCR. HPV-positive women underwent biopsy and endocervical curettage. Associations were determined using bivariate analysis and logistic regression.ResultsHPV and self-reported HIV prevalence were 39.0% and 9.2%, respectively. Eighteen (9.3%) CIN2+ lesions were found among HPV-positive women. Housewives had a higher risk of being HPV infected (OR = 1.60, p = 0.010). HIV co-infection (aOR = 3.44, p < 0.001) and hormonal contraception (aOR = 1.97, p = 0.007) were associated with increased HPV prevalence. HPV-positive women who used condoms during sexual intercourse were at lower risk of CIN2+ (aOR = 0.15, p = 0.029). CIN2–3 lesions were found in women younger than 50 years, with a median age of 36 years (31–44). HPV-16/18-positive women had a 4.65-fold increased risk of CIN2+ (p = 0.015).ConclusionsYoung, single women and housewives were at higher risk of HPV infection. Preventive strategies for cervical cancer in low-resource settings should target women aged 30–50 years for HPV screening, and should focus treatment and follow-up on HPV-16/18-positive women. Further studies are needed to clarify if other risk factors require attention.     

A let-7 microRNA polymorphism in the KRAS 3′-UTR is prognostic in oropharyngeal cancer

IntroductionThis study aimed to investigate the effect of genetic polymorphisms in miRNA sequences, miRNA target genes and miRNA processing genes as additional biomarkers to HPV for prognosis in oropharyngeal squamous cell carcinoma (OPSCC) patients. Secondarily, the prevalence of HPV-associated OPSCC in a European cohort was mapped.MethodsOPSCC patients (n = 122) were genotyped for ten genetic polymorphisms in pre-miRNAs (pre-mir-146a, pre-mir-196a2), in miRNA biosynthesis genes (Drosha, XPO5) and in miRNA target genes (KRAS, SMC1B). HPV status was assessed by p16 immunohistochemistry (IHC) and high-risk HPV in situ hybridization (ISH) or by p16 IHC and PCR followed by enzyme-immunoassay (EIA). Overall and disease specific survival were analysed using Kaplan–Meier plots (log-rank test). Cox proportional hazard model was used to calculate hazard ratios (HR).ResultsThe overall HPV prevalence rate in our Belgian/Dutch cohort was 27.9%. Patients with HPV⁺ tumours had a better 5-years overall survival (78% vs. 46%, p = 0.001) and a better 5-years disease specific survival (90% vs. 70%, p = 0.016) compared to patients with HPV⁻ tumours. In multivariate Cox analysis including clinical, treatment and genetic parameters, HPV negativity (HR = 3.89, p = 0.005), advanced T-stage (HR = 1.81, p = 0.050), advanced N-stage (HR = 5.86, p = 0.001) and >10 pack-years of smoking (HR = 3.45, p = 0.012) were significantly associated with reduced overall survival. The variant G-allele of the KRAS-LCS6 polymorphism was significantly associated with a better overall survival (HR = 0.40, p = 0.031).ConclusionsOur results demonstrate that OPSCC patients with the KRAS-LCS6 variant have a better outcome and suggest that this variant may be used as a prognostic biomarker for OPSCC.     

Validation of a free software for unsupervised assessment of abdominal fat in MRI

PurposeTo demonstrate the accuracy of an unsupervised (fully automated) software for fat segmentation in magnetic resonance imaging. The proposed software is a freeware solution developed in ImageJ that enables the quantification of metabolically different adipose tissues in large cohort studies.MethodsThe lumbar part of the abdomen (19 cm in craniocaudal direction, centered in L3) of eleven healthy volunteers (age range: 21–46 years, BMI range: 21.7–31.6 kg/m²) was examined in a breath hold on expiration with a GE T1 Dixon sequence. Single-slice and volumetric data were considered for each subject. The results of the visceral and subcutaneous adipose tissue assessments obtained by the unsupervised software were compared to supervised segmentations of reference. The associated statistical analysis included Pearson correlations, Bland-Altman plots and volumetric differences (VD_%).ResultsValues calculated by the unsupervised software significantly correlated with corresponding supervised segmentations of reference for both subcutaneous adipose tissue – SAT (R = 0.9996, p < 0.001) and visceral adipose tissue – VAT (R = 0.995, p < 0.001). Bland-Altman plots showed the absence of systematic errors and a limited spread of the differences. In the single-slice analysis, VD_% were (1.6 ± 2.9)% for SAT and (4.9 ± 6.9)% for VAT. In the volumetric analysis, VD_% were (1.3 ± 0.9)% for SAT and (2.9 ± 2.7)% for VAT.ConclusionsThe developed software is capable of segmenting the metabolically different adipose tissues with a high degree of accuracy. This free add-on software for ImageJ can easily have a widespread and enable large-scale population studies regarding the adipose tissue and its related diseases.     

Obesity,physical activity and cancer risks: Results from the Cancer,Lifestyle and Evaluation of Risk Study (CLEAR)

IntroductionPhysical activity (PA) has been associated with lower risk of cardiovascular diseases, but the evidence linking PA with lower cancer risk is inconclusive. We examined the independent and interactive effects of PA and obesity using body mass index (BMI) as a proxy for obesity, on the risk of developing prostate (PC), postmenopausal breast (BC), colorectal (CRC), ovarian (OC) and uterine (UC) cancers.MethodsWe estimated odds ratios (OR) and 95% confidence intervals (CI), adjusting for cancer specific confounders, in 6831 self-reported cancer cases and 1992 self-reported cancer-free controls from the Cancer Lifestyle and Evaluation of Risk Study, using unconditional logistic regression.ResultsFor women, BMI was positively associated with UC risk; specifically, obese women (BMI ≥30 kg/m²) had nearly twice the risk of developing UC compared to women with healthy-BMI-range (<25 kg/m²) (OR = 1.99;CI:1.31–3.03). For men, BMI was also positively associated with the risk of developing any cancer type, CRC and PC. In particular, obese men had 37% (OR = 1.37;CI:1.11–1.70), 113% (OR = 2.13;CI:1.55–2.91) and 51% (OR = 1.51;CI:1.17-1.94) higher risks of developing any cancer, CRC and PC respectively, when compared to men with healthy-BMI-range (BMI<25 kg/m²).Among women, PA was inversely associated with the risks of CRC, UC and BC. In particular, the highest level of PA (versus nil activity) was associated with reduced risks of CRC (OR = 0.60;CI:0.44–0.84) and UC (OR = 0.47;CI:0.27–0.80). Reduced risks of BC were associated with low (OR = 0.66;CI:0.51–0.86) and moderate (OR = 0.72;CI:0.57–0.91) levels of PA. There was no association between PA levels and cancer risks for men.We found no evidence of an interaction between BMI and PA in the CLEAR study.ConclusionThese findings suggest that PA and obesity are independent cancer risk factors.     

Performances de la TEP au 18F-FDG dans la caractérisation initiale de la lésion primitive du cancer du sein

Objective¹⁸F-FDG PET/CT is for the moment not recommended for stage T of the TNM classification of breast cancer. The aim of our study was to evaluate the performance of ¹⁸F-FDG PET/CT in the initial staging of breast tumors. Tumor size, skin involvement and inflammation as well as the relationship between primary tumor maximum standardized uptake value (SUVmax) and histopathological grade (SBR), molecular tumor subtypes (luminal A and B, Her2 enriched, triple negative), estrogen receptors (ER), progesterone receptors (PR) and focality were evaluated.MethodsHistological reports of patients operated for breast cancer, without neoadjuvant chemotherapy, were compared to preoperative ¹⁸F-FDG PET/CT.ResultsSeventy-four patients who underwent surgery in 2016 were included. ¹⁸F-FDG PET/CT was able to visualize primary tumors in 91% and to correctly classify the T stage of the TNM classification in 81% of the cases, to detect multifocality in 73% and cutaneous and inflammatory breast cancers in 100%. The uptake intensity of ¹⁸F-FDG (SUVmax) was significantly correlated with histo-prognostic factors such as SBR grade (P = 0.02), lack of expression of estrogen receptors (ER) (P = 0.01) and progesterone (PR) (P = 0.02), positive HER2 status (P = 0.01) or triple negative subtype tumors (P = 0.02).Conclusion¹⁸F-FDG PET/CT provides relevant elements for local assessment, in particular, tumor focality and inflammatory character in addition to ensuring the regional and extension assessment.     

Obesity and spinal loads; a combined MR imaging and subject-specific modeling investigation

Epidemiological studies have identified obesity as a possible risk factor for low back disorders. Biomechanical models can help test such hypothesis and shed light on the mechanism involved. A novel subject-specific musculoskeletal-modelling approach is introduced to estimate spinal loads during static activities in five healthy obese (BMI > 30 kg/m²) and five normal-weight (20 < BMI < 25 kg/m²) individuals. Subjects underwent T1 through S1 MR imaging thereby measuring cross-sectional-area (CSA) and moment arms of trunk muscles together with mass and center of mass (CoM) of T1-L5 segments. MR-based subject-specific models estimated spinal loads using a kinematics/optimization-driven approach. Average CSAs of muscles, moment arms of abdominal muscles, mass and sagittal moment arm of CoM of T1-L5 segments were larger in obese individuals (p < 0.05 except for the moment arm of CoMs) but moment arms of their back muscles were similar to those of normal-weight individuals (p > 0.05). Heavier subjects did not necessarily have larger muscle moment arms (e.g., they were larger in 64 kg (BMI = 20.7 kg/m²) subject than 78 kg (BMI = 24.6 kg/m²) subject) or greater T1-L5 trunk weight (e.g., the 97 kg (BMI = 31 kg/m²) subject had similar trunk weight as 109 kg (BMI = 33.3 kg/m²) subject). Obese individuals had in average greater spinal loads than normal-weight ones but heavier subjects did not necessarily have greater spinal loads (117 kg (BMI = 40.0 kg/m²) subject had rather similar L5-S1 compression as 105 kg (BMI = 34.7 kg/m²) subject). Predicted L4-L5 intradiscal pressures for the normal-weight subjects ranged close to the measured values (R² = 0.85–0.92). Obese individuals did not necessarily have greater IDPs than normal-weight ones.