Comparable Accuracy of Quantitative and Visual Analyses of [18F]FDG PET/CT for the Detection of Lymph Node Metastases from Head and Neck Squamous Cell Carcinoma.

BACKGROUND: In head and neck squamous cell carcinoma (HNSCC), [18F]FDG PET/CT is recommended for detecting recurrent disease and in the initial staging for evaluating distant metastases, but its use in detecting cervical lymph metastases remains unclear. The aim of this study is to evaluate and compare the diagnostic accuracy of [8F]FDG-PET/CT using visual and semi-quantitative analyses for detecting the nodal involvement in HNSCC. METHODS: We analyzed consecutive patients who underwent a preoperative [18F]FDG-PET/CT and neck dissection for HNSCC at our tertiary hospital. A blinded evaluation of the [18F]FDG uptake in each neck level was performed using a semi-quantitative approach (SUVmax and SUVR) and a visual grading system (uptake superior to the internal jugular vein for grade 1 and superior to the liver for grade 2). Analyses were compared to the histological results. RESULTS: In our 211 patients, analyses demonstrated similar diagnostic accuracy using a semi-quantitative approach or a visual grading system. Regarding the visual grading system, [18F]FDG-PET/CT detected nodal metastases with a specificity of 83% for lymph nodes classified as grade 1 and 98% for those classified as grade 2. The sensitivity was moderate, ranging from 60 to 63%. CONCLUSIONS: [18F]FDG PET/CT has a high specificity for detecting lymph node metastases in HNSCC and therefore must be considered in the nodal clinical staging.

Comparison between 2D FSE T2-weighted Dixon MRI and contrast-enhanced 2D FSE and 3D FSPGR T1-weighted Dixon MRI to quantify inflammation in hands of patients with early rheumatoid arthritis.

PURPOSE: The purpose of this study was to compare two-dimensional (2D) T2-weighted, contrast-enhanced 2D T1-weighted and contrast-enhanced three-dimensional (3D) T1-weighted Dixon MRI sequences to assess disease activity using the RAMRIS scoring system in hands of patients with early rheumatoid arthritis. MATERIALS AND METHODS: Twenty-five patients (19 women, 6 men; mean age 51.4 years ± 12.7 years [SD], age range: 28-70 years) with rheumatoid arthritis prospectively underwent MRI examination of both hands at 1.5 T using 2D fast spin-echo (FSE) T2-weighted, contrast-enhanced 2D FSE T1-weighted and contrast-enhanced 3D fast spoiled gradient echo (FSPGR) T1-weighted Dixon sequences. Three radiologists independently assessed disease activity according to RAMRIS using Dixon water-only and fat-only images. Intraclass correlation coefficients (ICC) were calculated to assess inter-technique and interobserver agreements. RESULTS: Agreement to assess total RAMRIS score was very good between the MRI protocols (mean ICC ranging from 0.81 to 0.93) and between readers (mean ICC ranging from 0.91 to 0.94). Mean total RAMRIS scores of the three readers were significantly greater with contrast-enhanced 3D FSPGR T1-weighted (42.73 ± 29.39) than with contrast-enhanced 2D FSE T1-weighted (35.81 ± 25.48) and 2D FSE T2-weighted (32.20 ± 25.06) Dixon sequences. CONCLUSION: 2D FSE T2-weighted, contrast-enhanced 2D FSE T1-weighted Dixon and contrast-enhanced 3D FSPGR T1-weighted Dixon protocols are reproducible alternatives for the RAMRIS scoring in hands of patients with early rheumatoid arthritis. Coupling contrast-enhanced 3D FSPGR T1-weighted and 2D FSE T2-weighted sequences might be the most efficient option to completely assess the rheumatoid arthritis -related synovial and bone changes with the Dixon method.

Comparison of intra- and inter-patient intensity standardization methods for multi-parametric whole-body MRI.

Objective.To test and compare different intensity standardization approaches for whole-body multi-parametric MR images, aiming to compensate voxel intensity differences between scans. These differences, common for magnetic resonance imaging, pose problems in image quantification, assessment of changes between a baseline and follow-up scan, and hinder performance of image processing and machine learning algorithms.Approach.In this work, we present a comparison on the accuracy of intensity standardization approaches with increasing complexity, for intra- and inter-patient multi-parametric whole-body MRI. Several approaches were used: z-scoring of the intensities, piecewise linear mapping and deformable mapping of intensity distributions into established reference intensity space. For each method, the impact on standardization algorithm on the use of single image or average population distribution reference; as well as, whole image and region of interest were additionally investigated. All methods were validated on a data set of 18 whole-body anatomical and diffusion-weighted MR scans consisting of baseline and follow-up examinations acquired from advanced prostate cancer patients and healthy volunteers.Main results.The piecewise linear intensity standardisation approach provided the best compromise between standardization accuracy and method stability, with average deviations in intensity profile of 0.011-0.027 and mean absolute difference of 0.29-0.37 standard score (intra-patient) and 0.014-0.056 (inter-patient), depending on the type of used MR modality.Significance.Linear piecewise approaches showed the overall best performance across multiple validation metrics, mostly because of its robustness. The inter-patient standardization proved to perform better when using population average reference image; in contrary to intra-patient approach, where the best results were achieved by standardizing towards a reference image taken as the baseline scan.

Whole-body MRI in oncology: can a single anatomic T2 Dixon sequence replace the combination of T1 and STIR sequences to detect skeletal metastasis and myeloma?

OBJECTIVES: To compare the diagnostic accuracy of a single T2 Dixon sequence to the combination T1+STIR as anatomical sequences used for detecting tumoral bone marrow lesions in whole-body MRI (WB-MRI) examinations. METHODS: Between January 2019 and January 2020, seventy-two consecutive patients (55 men, 17 women, median age = 66 years) with solid (prostate, breast, neuroendocrine) cancers at high risk of metastasis or proven multiple myeloma (MM) prospectively underwent a WB-MRI examination including coronal T1, STIR, T2 Dixon and axial diffusion-weighted imaging sequences. Two radiologists independently assessed the combination of T1+STIR sequences and the fat+water reconstructions from the T2 Dixon sequence. The reference standard was established by consensus reading of WB-MRI and concurrent imaging available at baseline and at 6 months. Repeatability and reproducibility of MRI scores (presence and semi-quantitative count of lesions), image quality (SNR: signal-to-noise, CNR: contrast-to-noise, CRR: contrast-to-reference ratios), and diagnostic characteristics (Se: sensitivity, Sp: specificity, Acc: accuracy) were assessed per-skeletal region and per-patient. RESULTS: Repeatability and reproducibility were at least good regardless of the score, region, and protocol (0.67 ≤ AC1 ≤ 0.98). CRR was higher on T2 Dixon fat compared to T1 (p < 0.0001) and on T2 Dixon water compared to STIR (p = 0.0128). In the per-patient analysis, Acc of the T2 Dixon fat+water was higher than that of T1+STIR for the senior reader (Acc = +0.027 [+0.025; +0.029], p < 0.0001) and lower for the junior reader (Acc = -0.029 [-0.031; -0.027], p < 0.0001). CONCLUSIONS: A single T2 Dixon sequence with fat+water reconstructions offers similar reproducibility and diagnostic accuracy as the recommended combination of T1+STIR sequences and can be used for skeletal screening in oncology, allowing significant time-saving. KEY POINTS: • Replacement of the standard anatomic T1 + STIR WB-MRI protocol by a single T2 Dixon sequence drastically shortens the examination time without loss of diagnostic accuracy. • A protocol based on fat + water reconstructions from a single T2 Dixon sequence offers similar inter-reader agreement and a higher contrast-to-reference ratio for detecting lesions compared to the standard T1 + STIR protocol. • Differences in the accuracy between the two protocols are marginal (+ 3% in favor of the T2 Dixon with the senior reader; -3% against the T2 Dixon with the junior reader).

Collapse-related bone changes at multidetector CT in ARCO 1-2 osteonecrotic femoral heads: correlation with clinical and MRI data.

OBJECTIVE: To assess the frequency of collapse-related bone changes at multi-detector CT (MDCT) in osteonecrotic femoral heads (ONFH) and to compare clinical parameters and MRI findings in Association Research Circulation Osseous (ARCO) 1-2 ONFH with or without collapse-related bone changes (CRBC) at MDCT. MATERIALS AND METHODS: This is a secondary analysis of radiographic, MRI, and MDCT examinations of ONFH of patients eligible for a prospective clinical trial. Radiographs and MRI were analyzed to perform ARCO staging. Frequency of CRBC at MDCT including cortical interruption, trabecular interruption, impaction, and resorption was determined by two readers (R1, R2) blinded to radiographic, MRI, and clinical data. Baseline clinical and imaging data of ARCO 1-2 ONFH were compared between hips with or without CRBC at MDCT. RESULTS: One hundred thirty-two hips of 77 participants were analyzed. There were 78 non-collapsed and 54 collapsed ONFH. For R1 and R2, 31/78 (40%) and 20/78 (26%) ARCO 1-2 ONFH and 54/54 (100%) and 53/54 (98%) ARCO 3-4 ONFH showed at least one CRBC at MDCT. For both readers, there was no significant difference in pain, functional impairment, size of lesion, and the presence of BME on MRI between ARCO 1-2 hips with or without CRBC at MDCT. CONCLUSION: Twenty-six to forty percent of ARCO 1-2 ONFH demonstrate at least one collapse-related bone change at CT. Their clinical and MRI findings do not differ from those without collapse-related bone changes. KEY POINTS: • Ninety-eight to one hundred percent of collapsed and 26-40% of non-collapsed osteonecrotic femoral heads presented at least one collapse-related bone change at CT (cortical or trabecular bone interruption, trabecular bone impaction, or resorption). • There was no significant difference in age, sex, pain, functional impairment, size of lesion, or frequency of marrow edema on MRI between non-collapsed hips with or without collapse-related bone changes at CT. • The significance of collapse-related bone changes at CT should be further assessed.

The Use of Medical Imaging Request Forms as Trigger Tools to Detect Intra-Hospital Adverse Events: A Pilot Study.

Aim: To evaluate the contribution of medical imaging request forms as trigger tools to detect patient adverse event (AE) occurring during hospitalization. Material and Methods: This is a retrospective study in a single institution. Between January and June 2019, the hospital information system (HIS) was fetched for request forms of radiological examinations performed for inpatients >48 hours after the admission date. The investigated request forms were: Doppler ultrasound of the upper limbs, Doppler ultrasound of the lower limbs, and the repetition of three consecutive requests of chest radiographs within 24 hrs, to detect upper or lower limb venous thrombosis, or AEs related to the respiratory system, respectively. Patients' medical charts and radiological examinations were evaluated to document the presence or absence of an AE. The frequencies of AEs in the three groups of trigger tools were compared to corresponding control groups, matched according to age, sex and length of stay. Results: Among a total of 2798 hospital admissions during the study period, there were 74 files triggered by the three types of radiological request forms. There were 6/24 AE (25%) related to upper limb venous thrombosis, 4/33 (12.1%) AE related to lower limb venous thrombosis, and 6/17 (35.3%) AE related to the respiratory system. For all the trigger tools, the frequency of AE in the study groups was significantly higher than that in the control groups. Conclusion: Medical imaging requests could be used as potential trigger tools to detect adverse events related to hospital stay.

Collapse-Related Bone Changes in Osteonecrotic Femoral Heads at Multidetector CT: Comparison between Femoral Heads with Limited and Advanced Collapse.

Aim: To assess the frequency of bone changes in resected osteonecrotic femoral head (ONFH) specimens at multidetector computed tomography (MDCT) and compare their frequencies between ONFH with limited or advanced collapse. Method: Fourteen ONFH were imaged using MDCT (n = 14) and microcomputed tomography ([µCT]; n = 8). Preoperative staging was performed using radiographs and MRI. Coronal reformats of MDCT images of the specimens were analyzed using the grid overlay method. There were 2,933 grid boxes containing cortical bone and 10,596 containing trabecular bone. Two MSK radiologists assessed in every grid box the presence of interface-related sclerosis, cortical bone interruption, trabecular bone interruption, and trabecular bone resorption. The frequency of grid boxes with bone changes at MDCT was calculated and compared between ONFH with limited (<1.5 mm) or advanced (≥1.5 mm) collapse. Results: For both readers R1 and R2, there were 1111/10596 (10.5%) and 1362/10596 (12.9%) grid boxes with interface-related bone sclerosis, 557/2933 (19%) and 413/2933 (14.1%) with cortical bone interruption, 796/10596 (7.5%) and 665/10596 (6.3%) with trabecular bone interruption, and 331/10596 (3.1%) and 595/10596 (5.6%) with trabecular bone resorption. The frequency of grid boxes with cortical interruption and trabecular bone resorption was significantly higher in ONFH with advanced than in ONFH with limited collapse. There was no significant difference in frequency of grid boxes with trabecular interruption and interface-related bone sclerosis between ONFH with advanced or limited collapse. Conclusion: Cortical interruption and trabecular resorption, but not trabecular interruption, were more frequent in osteonecrotic femoral heads with advanced than with limited collapse.

Whole Body MRI in the Detection of Lymph Node Metastases in Patients with Testicular Germ Cell Cancer.

Whole-Body Magnetic Resonance Imaging (WB-MRI) is increasingly used for metastatic screening in oncology. This prospective single center study assesses the diagnostic value of WB-MRI including diffusion weighted imaging (DWI) and identifies the sufficient protocol for metastatic lymph node detection in patients with testicular germ cell cancer (TGCC). Forty-three patients underwent contrast enhanced thoraco-abdominopelvic CT (TAP-CT) and WB-MRI with DWI for metastatic lymph node screening. Two independent readers reviewed CTs and WB-MRIs. The diagnostic performance of different imaging protocols (CT, complete WB-MRI, T1W + DWI, T2W + DWI), the agreement between these protocols and the reference standard, the reproducibility of findings and the image quality (Signal and contrast to Noise Ratios, Likert scale) were studied. Reproducibility was very good regardless of both lesion locations (retroperitoneal vs distant lymph nodes, other lesions) and the reader. Diagnostic accuracy of MRI was ≥95% (regardless of the locations and imaging protocol); accuracy of CT was ≥93%. There was a strict overlap of 95% CIs associated with this accuracy between complete WB-MRI, T1W + DWI and T2W + DWI, regardless of the reader. Higher Likert score and SNR were observed for DWI, followed by T2W and T1W sequences. In conclusion, a fast WB-MRI protocol including T2W and DWI is a sufficient, accurate, non-irradiating alternative to TAP-CT for metastatic lymph node screening in TGCC.

MRI of Hands with Early Rheumatoid Arthritis: Usefulness of Three-Point Dixon Sequences to Quantitatively Assess Disease Activity.

The use of efficient treatment with a treat-to-target strategy combined with early detection of the disease completely changed the imaging presentation and outcome of newly diagnosed rheumatoid arthritis (RA) patients. Magnetic Resonance Imaging (MRI) has become the reference technique in clinical research to detect and quantify inflammatory involvement of the soft tissues (synovitis and tenosynovitis) and bone marrow (osteitis) along with structural damages of the bone (erosions) in hands of patients with RA. Three-point Dixon MRI may be a valuable alternative to the currently recommended sequences as it yields effective fat signal suppression, high imaging quality and reproducible assessment of disease activity.

India ink artifact on Dixon out-of-phase images can be used as a landmark to measure joint space width at MRI.

PURPOSE: The purpose of this study was to test the feasibility of joint space width (JSW) measurement on Dixon MR images with the "India ink" artifact between cartilage and bone marrow as a landmark for the subchondral plate and to correlate it with radiographic JSW. MATERIALS AND METHODS: Both hands of six volunteers (three women, three men; mean age, 36.7 ± 10.4 [SD] years) and 24 patients with early rheumatoid arthritis (16 women, 8 men; mean age, 45.7 ± 14.5 [SD] years) were imaged with MRI Dixon sequences and radiographs. Two radiologists (R1, R2) separately measured JSW in 11 joints per hand on all Dixon images in volunteers, on contrast-enhanced T1-weighted out-of-phase images in patients and on radiographs in both groups. Inter-technique, intra-observer and inter-observer agreements were assessed using intraclass correlation coefficient (ICC) and Bland Altman analysis. RESULTS: In volunteers, agreement between JSW measurements on MRI and radiographs was the highest with T1-weighted Dixon out-of-phase images (mean ICC ranging from 0.69 to 0.76 for R1 and 0.65 to 0.74 for R2). In patients, median bias between JSW measurements at first and second readings was not statistically significantly different from 0 on T1-weighted Dixon out-of-phase images (mean bias of 0.00 and + 0.01 mm) and radiographs (mean bias of 0.00 and +0.01 mm). Median bias of the difference between measurements of R1 and R2 was statistically significantly different from 0 on T1-weighted Dixon out-of-phase images (mean bias of -0.11 and -0.09 mm; P < 0.039) and radiographs (mean bias of -0.24 and -0.20 mm; P < 0.035). CONCLUSION: Measurement of hand JSW on T1-weighted Dixon out-of-phase images using India ink artifact as a landmark for the subchondral plate is repeatable and reproducible.

Limited Performance of Estimated Total Kidney Volume for Follow-up of ADPKD.

INTRODUCTION: Total kidney volume (TKV) is a qualified biomarker for disease progression in autosomal dominant polycystic kidney disease (ADPKD). Recent studies suggest that TKV estimated using ellipsoid formula correlates well with TKV measured by manual planimetry (gold standard). We investigated whether the ellipsoid formula could replace manual planimetry for follow-up of ADPKD patients. METHODS: Abdominal magnetic resonance images of patients with ADPKD performed between January 1, 2013, and June 31, 2019, in Saint-Luc Hospital, Brussels, were used. Two radiologists independently performed manual TKV (mTKV) measures and kidney axial measures necessary for estimating TKV (eTKV) using ellipsoid equation. Repeatability and reproducibility of axial measures, mTKV and eTKV, and agreement between mTKV and eTKV were assessed (Bland-Altman). Intraclass correlation coefficient (ICC) was used to assess agreement on Mayo Clinic Imaging Classification (MCIC) scores. RESULTS: 140 patients were included with mean age 45±13 years, estimated glomerular filtration rate (eGFR) 71±31 ml/min per 1.73 m2, and mTKV 1697±1538 ml. Repeatability and reproducibility were superior for mTKV versus eTKV (repeatability coefficient 2.4% vs. 14% in senior reader, and reproducibility coefficient 6.7% vs. 15%). Intertechnique reproducibility coefficient (95% confidence interval [CI]) was 19% (17%, 21%) in senior reader. Intertechnique agreement on derived MCIC scores was very good (ICC = 0.924 [0.884, 0.949]). CONCLUSION: TKV estimated using ellipsoid equation demonstrates poor repeatability and reproducibility compared with that of mTKV. Intertechnique agreement is also limited, even when measurements are performed by an experienced radiologist. Estimated TKV, however, accurately determines MCIC score.

Instability of the extensor digitorum tendons in Jaccoud arthropathy assessed by semi-dynamic MRI of the metacarpophalangeal joints.

PURPOSE: The purpose of this study was to test the hypothesis that Jaccoud arthropathy (JA) in patients with systemic lupus erythematosus (SLE) is associated with instability of the extensor digitorum (ED) tendons during flexion of the metacarpophalangeal (MCP) joints by comparing the position of the ED tendons between SLE patients with JA and control subjects on hand MRI obtained with flexed and extended MCP joints. MATERIALS AND METHODS: Thirty-two hands of SLE patients with JA (13 women and 3 men; mean age, 50.0±12.2 [SD] years; age range: 26-68years) and 24 hands of sex- and age-matched control subjects (20 women and 4 men; mean age, 50.1±13.0 [SD] years; age range: 24-68years) were included in the study. Axial spin echo T1-weighted MRI images of the second to fifth MCP joints in flexion and in extension were obtained. Two radiologists (R1 and R2) separately measured the amplitude and assessed the direction of the displacement of the ED tendons with respect to the midline at the level of each MCP joint. Statistical analysis included two-way ANOVA with random effects to assess differences in amplitude and Fisher-Freeman-Halton exact test to assess differences in direction with P-values<0.0083 and<0.0063 considered as statistically significant respectively. RESULTS: Amplitude of the displacement of the ED tendons was statistically significantly greater in SLE patients with JA than in control subjects in flexion for both readers (median 58°, 95% confidence interval [CI]: 50°-65° vs. 20°, 95% CI: 16°-24°; P<0.0001 for R1 and 54°, 95% CI: 47°-61° vs. 25°, 95% CI: 22°-28°; P<0.0001 for R2) and in extension for one reader (17°, 95% CI: 15°-20° vs. 14°, 95% CI: 11°-16°; P=0.0048 for R1 and 20°, 95% CI: 15°-25° vs. 16°, 95% CI: 12°-18°; P=0.0292 for R2). Ulnar deviation of the ED tendons was statistically significantly more frequent in SLE patients with JA than in control subjects in flexion and in extension for both readers (P<0.0001). CONCLUSION: JA is associated with instability of the ED tendons in patients with SLE best depicted when MCP joints are flexed.

Semi-quantitative CT scoring of nailed shaft fractures during normal healing and in non-unions: comparison with radiographic scoring.

PURPOSE: To compare tomographic (TUS) with radiographic (RUS) union scores in nailed shaft fractures during normal healing and in non-unions. METHODS: Two radiologists blinded to fracture age separately determined RUS and TUS in nailed femoral or tibial shaft fractures by analyzing the radiographic and CT examinations obtained in 47 patients during normal healing (early fracture group; 24 study participants, 17 men,19 tibias, mean fracture-CT delay 109 ±â€¯57 days [42-204 days]) and in surgically proven non-united fractures (late fracture group, 23 patients, 14 men, 12 tibias, mean fracture-CT delay 565 ±â€¯519 days[180-1983 days]). In both study groups, we determined the inter- and intra-observer agreement of RUS and TUS and compared TUS with RUS. RESULTS: Intra- and inter-observer agreement of RUS and TUS was very good in the early fracture group and good in the late fracture group for both readers. TUS correlated with RUS substantially in the early fracture group and only weakly in the late fracture group. TUS was statistically significantly lower than RUS in study participants with RUS ≥ 8 or 9 for R2 only and ≥ 10 for both readers in the early fracture group and in patients with RUS ≥ 8, 9 or 10 in the late fracture group for both readers. CONCLUSION: RUS and TUS of nailed shaft fractures during normal healing or in non-unions are both feasible and reproducible. They yield similar values in fractures with no or limited callus. TUS yields lower values than RUS in fractures with callus.

Contrast-enhanced T1-weighted Dixon water- and fat-only images to assess osteitis and erosions according to RAMRIS in hands of patients with early rheumatoid arthritis.

PURPOSE: To assess the agreement between readers using contrast-enhanced T1-weighted Dixon water- and fat-only images and OMERACT-recommended sequences for the scoring of osteitis and erosions according to the rheumatoid arthritis (RA) MRI scoring system (RAMRIS) in hands of patients with early RA. MATERIALS AND METHODS: Both hands of 24 patients (16 women, 8 men; mean age, 45.7±14.5 [SD] years; age range: 25-70 years) with early RA were prospectively imaged with fat-saturated T2-weighted sequences, non-Dixon T1-weighted imaging prior to contrast material injection and T1-weighted Dixon imaging after contrast material injection at 1.5T. There were Two radiologists separately quantified osteitis and erosions according to RAMRIS using contrast-enhanced T1-weighted Dixon water-only and fat-saturated T2-weighted images for osteitis and contrast-enhanced T1-weighted Dixon fat-only and T1-weighted images prior to contrast material injection for erosions. Intraclass correlation coefficients (ICC) were calculated to assess inter-technique, intra-observer and inter-observer agreement. RESULTS: Mean ICC for the agreement between Dixon and non-Dixon images ranged from 0.68 (95%CI: 0.20-0.90) to 0.99 (95%CI: 0.95-1.00) for the scoring of osteitis and from 0.77 (95%CI: 0.38-0.93) to 0.99 (95%CI: 0.95-1.00) for the scoring of erosions. Mean ICC for the agreement between first and second readings ranged from 0.94 (95%CI: 0.81-0.98) to 0.97 (95%CI: 0.91-0.99) for the scoring of osteitis using Dixon and 0.91 (95%CI: 0.72-0.97) to 0.98 (95%CI: 0.92-0.99) using non-Dixon images and from 0.80 (95%CI: 0.45-0.94) to 0.97 (95%CI: 0.91-0.99) for the scoring of erosions using Dixon and 0.72 (95%CI: 0.29-0.91) to 0.98 (95%CI: 0.92-0.99) using non-Dixon images. CONCLUSION: Contrast-enhanced T1-weighted Dixon water- and fat-only images can serve as an alternative to fat-saturated T2-weighted and T1-weighted MRI sequences for the assessment of osteitis and erosions according to the RAMRIS scoring system in hands of patients with early RA.

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.

Incorporating radiomics into clinical trials: expert consensus endorsed by the European Society of Radiology on considerations for data-driven compared to biologically driven quantitative biomarkers.

Existing quantitative imaging biomarkers (QIBs) are associated with known biological tissue characteristics and follow a well-understood path of technical, biological and clinical validation before incorporation into clinical trials. In radiomics, novel data-driven processes extract numerous visually imperceptible statistical features from the imaging data with no a priori assumptions on their correlation with biological processes. The selection of relevant features (radiomic signature) and incorporation into clinical trials therefore requires additional considerations to ensure meaningful imaging endpoints. Also, the number of radiomic features tested means that power calculations would result in sample sizes impossible to achieve within clinical trials. This article examines how the process of standardising and validating data-driven imaging biomarkers differs from those based on biological associations. Radiomic signatures are best developed initially on datasets that represent diversity of acquisition protocols as well as diversity of disease and of normal findings, rather than within clinical trials with standardised and optimised protocols as this would risk the selection of radiomic features being linked to the imaging process rather than the pathology. Normalisation through discretisation and feature harmonisation are essential pre-processing steps. Biological correlation may be performed after the technical and clinical validity of a radiomic signature is established, but is not mandatory. Feature selection may be part of discovery within a radiomics-specific trial or represent exploratory endpoints within an established trial; a previously validated radiomic signature may even be used as a primary/secondary endpoint, particularly if associations are demonstrated with specific biological processes and pathways being targeted within clinical trials. KEY POINTS: • Data-driven processes like radiomics risk false discoveries due to high-dimensionality of the dataset compared to sample size, making adequate diversity of the data, cross-validation and external validation essential to mitigate the risks of spurious associations and overfitting. • Use of radiomic signatures within clinical trials requires multistep standardisation of image acquisition, image analysis and data mining processes. • Biological correlation may be established after clinical validation but is not mandatory.

Comparison between 3-point Dixon- and CHESS-based OMERACT-recommended MRI protocols in hands of patients with suspicion of early rheumatoid arthritis.

PURPOSE: To compare fat suppression effectiveness, image quality and disease activity scores between MRI protocols based on the Dixon method and the Chemical Shift Selective (CHESS) technique in hands of patients with suspicion of early rheumatoid arthritis (RA). METHOD: Both hands of 28 patients (19 women; mean age 45.2 years old) with suspicion of early RA were prospectively imaged with Dixon- and CHESS-based OMERACT recommended protocols at 1.5 T including fat-suppressed T2-weighted and contrast-enhanced T1-weighted imaging. Two radiologists (R1/R2) separately assessed effectiveness of fat suppression and determined RAMRIS scores woth the Dixon- and CHESS-based protocols. R1 repeated the RAMRIS scoring and measured contrast-to-noise ratios (CNRs) on Dixon and CHESS images. Statistics included 2-way ANOVA test for the comparison of CNRs and Bland-Altman methodology for inter-technique and intra-observer agreement (p < 0.05). RESULTS: Fat suppression failure occurred in up to 1 patient with the Dixon- and 25 patients with the CHESS-based protocols. CNRs were significantly higher on T1-weighted and lower on T2-weighted Dixon images than on the corresponding CHESS images (p ≤ 0.042). Median bias of the difference between Dixon- and CHESS-based RAMRIS scores was not significantly different from 0 (-0.8 to +1.0 and -1.1 to +1.4 for R1/R2). Median bias of the difference between RAMRIS scores at first and second readings was significantly different from 0 with the CHESS-based protocols (-0.8 to +1.7) but not with the Dixon-based protocols (+0.0 to +1.0). CONCLUSIONS: Dixon sequences yield more effective fat suppression and more reproducible RAMRIS scoring than CHESS sequences in hands with suspicion of early RA.

Preventive Moderate Continuous Running-Exercise Conditioning Improves the Healing of Non-Critical Size Bone Defects in Male Wistar Rats: A Pilot Study Using µCT.

Although physical exercise has unquestionable benefits on bone health, its effects on bone healing have been poorly investigated. This study evaluated the effects of preemptive moderate continuous running on the healing of non-critical sized bone defects in rats by µCT. We hypothesized that a preemptive running exercise would quicken bone healing. Twenty 5-week-old, male, Wistar rats were randomly allocated to one of the following groups (n = 10): sedentary control (SED) or continuous running (EX, 45 min/d, 5 d/week at moderate speed, for 8 consecutive weeks). A 2 mm diameter bone defect was then performed in the right tibia and femur. No exercise was performed during a 4 week-convalescence. Healing-tissue trabecular microarchitectural parameters were assessed once a week for 4 weeks using µCT and plasma bone turnover markers measured at the end of the study protocol (time point T12). At T12, bone volume fraction (BV/TV; BV: bone volume, TV: tissue volume) of the healing tissue in tibiae and femurs from EX rats was higher compared to that in SED rats (p = 0.001). BV/TV in EX rats was also higher in tibiae than in femurs (p < 0.01). The bone mineral density of the healing tissue in femurs from EX rats was higher compared to that in femurs from SED rats (p < 0.03). N-terminal telopeptide of collagen type I in EX rats was decreased compared to SED rats (p < 0.05), while no differences were observed for alkaline phosphatase and parathyroid hormone. The study provides evidence that preemptive moderate continuous running improves the healing of non-critical sized bone defects in male Wistar rats.

Topology of microfractures in osteonecrotic femoral heads at µCT and histology.

AIM: To assess the topology of bone and cartilage microfractures in osteonecrotic femoral heads. METHOD: Sixteen resected human femoral heads with collapsed osteonecrosis (ON, n = 11) or osteoarthritis (OA, n = 5) were imaged at µCT with 12 µ nominal resolution. Forty-seven histological sections and µCT reformats with (n = 30) or without (8 from ON and 9 from OA femoral heads) osteonecrotic lesions were obtained and divided in 2 × 2 mm segments by a superposed grid. A radiologist and a pathologist separately assessed the presence of bone and cartilage microfractures in each segment on µCT and histological images, respectively. We determined the frequency and distribution of segments with bone microfractures according to a zonal distribution. Matrix analysis was performed by using Matlab to calculate the connectivity index and long/short axis ratios of clustered segments with microfractures. RESULTS: Segments with bone microfractures but not with cartilage microfractures were found more frequently in ON than in OA femoral heads. In the 38 matched µCT and histological images from ON femoral heads, 86%/82% of segments with cortical microfracture, 91%/96% of segments with trabecular microfractures involved ON lesions at µCT/histology. At histology, 83% of segments with cartilage microfractures involved ON lesions. In the 30 paired µCT and histological images containing necrotic lesions, the frequency of segments with trabecular microfractures in the superficial layers (55% at µCT/51% at histology) was statistically significantly higher than in the deep layer (25% P < 0.0001/35%; P = 0.0006). Clustered segments with cortical/trabecular microfractures, exclusively found in osteonecrotic lesions, had a connectivity index >2.0/20.0 and mean long/short axis ratio > 2.35/2.2, respectively. CONCLUSION: Segments with bone microfractures predominate in necrotic lesions. Segments with trabecular microfractures form elongated clusters near the femoral head surface.