Repeatability and reproducibility of ADC measurements: a prospective multicenter whole-body-MRI study.

OBJECTIVES: Multicenter oncology trials increasingly include MRI examinations with apparent diffusion coefficient (ADC) quantification for lesion characterization and follow-up. However, the repeatability and reproducibility (R&R) limits above which a true change in ADC can be considered relevant are poorly defined. This study assessed these limits in a standardized whole-body (WB)-MRI protocol. METHODS: A prospective, multicenter study was performed at three centers equipped with the same 3.0-T scanners to test a WB-MRI protocol including diffusion-weighted imaging (DWI). Eight healthy volunteers per center were enrolled to undergo test and retest examinations in the same center and a third examination in another center. ADC variability was assessed in multiple organs by two readers using two-way mixed ANOVA, Bland-Altman plots, coefficient of variation (CoV), and the upper limit of the 95% CI on repeatability (RC) and reproducibility (RDC) coefficients. RESULTS: CoV of ADC was not influenced by other factors (center, reader) than the organ. Based on the upper limit of the 95% CI on RC and RDC (from both readers), a change in ADC in an individual patient must be superior to 12% (cerebrum white matter), 16% (paraspinal muscle), 22% (renal cortex), 26% (central and peripheral zones of the prostate), 29% (renal medulla), 35% (liver), 45% (spleen), 50% (posterior iliac crest), 66% (L5 vertebra), 68% (femur), and 94% (acetabulum) to be significant. CONCLUSIONS: This study proposes R&R limits above which ADC changes can be considered as a reliable quantitative endpoint to assess disease or treatment-related changes in the tissue microstructure in the setting of multicenter WB-MRI trials. KEY POINTS: • The present study showed the range of R&R of ADC in WB-MRI that may be achieved in a multicenter framework when a standardized protocol is deployed. • R&R was not influenced by the site of acquisition of DW images. • Clinically significant changes in ADC measured in a multicenter WB-MRI protocol performed with the same type of MRI scanner must be superior to 12% (cerebrum white matter), 16% (paraspinal muscle), 22% (renal cortex), 26% (central zone and peripheral zone of prostate), 29% (renal medulla), 35% (liver), 45% (spleen), 50% (posterior iliac crest), 66% (L5 vertebra), 68% (femur), and 94% (acetabulum) to be detected with a 95% confidence level.

Sonographic and radiographic evaluation of the extensor tendons in early postoperative period after total knee arthroplasty.

OBJECTIVE: To prospectively assess the early changes in the quadriceps and patellar tendons before and after total knee arthroplasty using ultrasound, shear wave elastography, and X-rays. MATERIALS AND METHODS: Radiographs, ultrasound, and shear wave elastography were performed on 23 patients (16 women; aged 51-85, mean 66 ± 9 years) before and after surgery at 6 weeks and on 11 patients at 3 months. Patellar position and patellar tendon lengths were evaluated by radiography; joint effusion or synovitis, quadriceps and patellar tendon lengths, and thicknesses, echogenicity, vascularity, and stiffness were assessed with ultrasound and shear wave elastography. RESULTS: In the early postoperative period, 87% of the patients had joint effusion, and 43% had signs of synovitis. There was a significant thickening of the quadriceps tendon in 51.5% (p < .0001) and of the patellar tendon in 93.8% (p < .0001) of patients with a significant shortening of the patellar tendon in 7.8% (p < .0001). A hypoechoic defect on the medial aspect of the quadriceps tendon was found in 87% of the patients. There was a significant increase in Young's modulus in the quadriceps tendon (p = .0006) but not in the patellar tendon. CONCLUSION: The following should not be considered to be pathological findings at early postoperative imaging: joint effusion, synovitis, increasing of stiffness and thickening of quadriceps tendons by more than 50%, thickening of patellar tendon by more than 90%, focal defect through the medial aspect of the quadriceps tendon, and shortening of the patellar tendon by 8%.

The central vein sign in multiple sclerosis patients with vascular comorbidities.

BACKGROUND: The central vein sign (CVS) is an imaging biomarker able to differentiate multiple sclerosis (MS) from other conditions causing similar appearance lesions on magnetic resonance imaging (MRI), including cerebral small vessel disease (CSVD). However, the impact of vascular risk factors (VRFs) for CSVD on the percentage of CVS positive (CVS+) lesions in MS has never been evaluated. OBJECTIVE: To investigate the association between different VRFs and the percentage of CVS+ lesions in MS. METHODS: In 50 MS patients, 3T brain MRIs (including high-resolution 3-dimensional T2*-weighted images) were analyzed for the presence of the CVS and MRI markers of CSVD. A backward stepwise regression model was used to predict the combined predictive effect of VRF (i.e. age, hypertension, diabetes, obesity, ever-smoking, and hypercholesterolemia) and MRI markers of CSVD on the CVS. RESULTS: The median frequency of CVS+ lesions was 71% (range: 35%-100%). In univariate analysis, age (p < 0.0001), hypertension (p < 0.001), diabetes (p < 0.01), obesity (p < 0.01), smoking (p < 0.05), and the presence of enlarged-perivascular-spaces on MRI (p < 0.005) were all associated with a lower percentage of CVS+ lesions. The stepwise regression model showed that age and arterial hypertension were both associated with the percentage of CVS+ lesions in MS (adjusted R2 = 0.46; p < 0.0001 and p = 0.01, respectively). CONCLUSION: The proportion of CVS+ lesions significantly decreases in older and hypertensive MS patients. Although this study was conducted in patients with an already established MS diagnosis, the diagnostic yield of the previously proposed 35% CVS proportion-based diagnostic threshold appears to be not affected. Overall these results suggest that the presence of VRF for CSVD should be taken into account during the CVS assessment.

Multi-atlas segmentation of the skeleton from whole-body MRI-Impact of iterative background masking.

PURPOSE: To improve multi-atlas segmentation of the skeleton from whole-body MRI. In particular, we study the effect of employing the atlas segmentations to iteratively mask tissues outside of the region of interest to improve the atlas alignment and subsequent segmentation. METHODS: An improved atlas registration scheme is proposed. Starting from a suitable initial alignment, the alignment is refined by introducing additional stages of deformable registration during which the image sampling is limited to the dilated atlas segmentation label mask. The performance of the method was demonstrated using leave-one-out cross-validation using atlases of 10 whole-body 3D-T1 images of prostate cancer patients with bone metastases and healthy male volunteers, and compared to existing state of the art. Both registration accuracy and resulting segmentation quality, using four commonly used label fusion strategies, were evaluated. RESULTS: The proposed method showed significant improvement in registration and segmentation accuracy with respect to the state of the art for all validation criteria and label fusion strategies, resulting in a Dice coefficient of 0.887 (STEPS label fusion). The average Dice coefficient for the multi-atlas segmentation showed over 11% improvement with a decrease of false positive rate from 28.3% to 13.2%. For this application, repeated application of the background masking did not lead to significant improvement of the segmentation result. CONCLUSIONS: A registration strategy, relying on the use of atlas segmentations as mask during image registration was proposed and evaluated for multi-atlas segmentation of whole-body MRI. The approach significantly improved registration and final segmentation accuracy and may be applicable to other structures of interest.

Assessment of response to chemotherapy in pancreatic ductal adenocarcinoma: Comparison between diffusion-weighted MR quantitative parameters and RECIST.

PURPOSE: To prospectively assess chemotherapy-induced changes in pancreatic ductal adenocarcinoma (PDA) with diffusion-weighted (DW)-MR quantitative metrics, including apparent diffusion coefficient (ADC) and histogram-derived parameters, compared with RECIST 1.1. METHODS: 24 patients underwent DW-MR at baseline, week-2 and week-8 after chemotherapy initiation. Tumour diameter was assessed on T2-weighted images. Regions-of-interest (ROI) were drawn on ADC map for ROI-ADC. Volume segmentation (b = 1000 s/mm2 images) provided DW-volume and histogram-derived diffusion parameters (H-ADC, H-D and H-PF). All variables and their relative change were compared to baseline or between responders and non-responders. Discriminant analysis was performed. RESULTS: 15/24 patients were responders. RECIST 1.1 correctly characterized 6/15 responders at week-8. At week-2, in responders DW-volume decreased (P = .002); ROI-ADC mean H-D increased (P = .047; P = .048;). The 25th percentile H-D increased in responders and decreased in non-responders (P = .016; P = .048). At week-8 in responders DW-volume decreased and ROI-ADC mean, 25th, 50th, 75th percentiles of H-ADC and H-D increased (P < .05). No changes were observed in non-responders (P > .05). At week-2, 25th percentile of H-D and H-PF relative change correctly classified 20/24 patients (P = .003); at week-8, DW-volume relative change correctly classified 22/24 patients (P < .0001). CONCLUSIONS: ROI-ADC, DW-volume and histogram-derived diffusion parameters are more accurate to categorize responding and non-responding PDA patients treated with chemotherapy compared with RECIST 1.1.

Absence of clinical cerebellar syndrome after serial injections of more than 20 doses of gadoterate, a macrocyclic GBCA: a monocenter retrospective study.

Sound evidence of gadolinium accumulation in brain has been recently provided after repeated administrations of linear gadolinium-based contrast agents (GBCAs), especially at the cerebellum level. Although data regarding brain accumulation of macrocyclic GBCAs are more reassuring, there is now a genuine concern ("gadolinium-phobia") about possible long-term consequences of gadolinium deposits, especially in terms of cerebellar sequelae. We, therefore, questioned about the clinical impact of serial administration of gadoterate meglumine, a macrocyclic GBCA. In this retrospective study (2000-2016) of medical files of patients who received more than 20 administrations of gadoterate, we searched for cerebellar symptoms and signs developing during the regular follow-up. We reviewed medical files of ten patients (mean age 34.4 ± 20.8 years; 4 males, 6 females) who received 28.2 ± 5.3 doses of gadoterate (average total dose of GBCA 518 ± 226 ml; range 185-785 ml). Patients were examined by at least two medical specialists depending on initial diagnosis, and at least once by a neurosurgeon. Mean follow-up time was 91 months (range 49-168) and six out of ten patients experienced new symptoms or signs. No clinician reported the appearance of a rising cerebellar syndrome, nor newly appeared symptoms or signs suggested cerebellar toxicity. This retrospective clinical study shows no de novo clinical cerebellar syndrome following repeated administrations of gadoterate. Our results argue against a cerebellar toxicity of this macrocyclic agent. Still, confirmation in a larger number of subjects is required, as well as clinical studies concerning linear GBCAs whose structure and in vivo stability are distinct.

Focal liver lesions detection: Comparison of respiratory-triggering, triggering and tracking navigator and tracking-only navigator in diffusion-weighted imaging.

PURPOSE: To compare low b value (10s/mm(2)) spin-echo echo-planar (SE-EP) diffusion-weighted imaging (DWI) acquired with respiratory-triggering (RT), triggering and tracking navigator (TT), tracking only navigator (TRON) techniques for image quality and focal liver lesions (FLL) detection in non-cirrhotic patients. MATERIAL AND METHODS: This bi-centric study was approved by the institutional review boards; informed consent was obtained. Eighty-three patients were prospectively included and SE-EP-DWI with RT, TT and TRON techniques were performed. DWI sequences were randomized and independently analyzed by two readers. The qualitative evaluation was based on a 3-point score for axial artifacts (motion, ghost, susceptibility artifacts and distortion) and stair-step artifacts. Sensitivity of FLL detection was calculated for all lesions together and after lesion size stratification (≤ 10 mm, >10-20mm and >20mm). The standard of reference consisted of a retrospective reading of the conventional MRI, the three DWI sequences and by follow-up (12 months): a total of 409 FLL were detected. Data between sequences was compared with non-parametric tests. Cohen's kappa coefficient was used for inter-observer agreement. RESULTS: Image quality was comparable for RT and TT. TRON showed statistically significantly more axial artifacts for the two readers (p<0.05). Stair-step artifacts were not statistically significantly different between DWI sequences. Overall sensitivities for RT, TT, TRON were 85%, 86%, 82% and 86%, 89% 83%, respectively, for readers 1 and 2. The inter-observer agreement was very good. CONCLUSION: Image quality was better for RT and TT compared to TRON. Overall sensitivities for FLL detection were comparable between techniques and readers.

Endometriosis: contribution of 3.0-T pelvic MR imaging in preoperative assessment--initial results.

PURPOSE: To determine the accuracy of 3.0-T pelvic magnetic resonance (MR) imaging in the preoperative assessment of endometriosis and to evaluate colon wall involvement after intrarectal gel administration. MATERIALS AND METHODS: Institutional review board approval for this study was obtained, and each patient gave written informed consent. Forty-one consecutive patients with clinical suspicion of endometriosis underwent pelvic MR imaging at 3.0 T before surgery. Single-shot and high-spatial-resolution axial T2-weighted, sagittal fat-suppressed T2-weighted, and axial fat-suppressed T1-weighted sequences were performed. T2-weighted sequences were repeated after the rectum was filled with ultrasonographic (US) gel. Two blinded readers interpreted images independently. Image quality was scored by using a four-point scale. Detailed mapping of deep endometriosis was performed. Colon wall infiltration was graded (none, serosa, muscularis, submucosa, mucosa). MR imaging results were compared with surgical and pathologic findings. Interobserver agreement was assessed by using kappa statistics. Nonparametric tests were performed to compare colon wall infiltration scores without and those with US gel and between observers. RESULTS: Twenty-seven of 41 patients had deep endometriosis at surgery and histopathologic examination. Sensitivity, specificity, positive and negative predictive values, and accuracy for the diagnosis of deep endometriosis at MR imaging were 96.3% (26 of 27), 100% (14 of 14), 100% (26 of 26), 93.3% (14 of 15), and 97.6% (40 of 41), respectively. kappa Values ranged from 0.65 to 1.0, depending on the location of deep endometriosis. Colon wall infiltration assessment by both readers correlated well with pathologic findings (Spearman coefficient, >0.93), although median wall involvement scores were lower at pathologic examination than for both readers both before (P = .042 and P = .011) and after (P = .079 and P = .011) intrarectal gel filling. CONCLUSION: MR imaging of the pelvis at 3.0 T is accurate in the diagnosis and staging of deep endometriosis for the preoperative assessment of patients clinically suspected of having endometriosis.