Screening HIV Patients at Risk for NAFLD Using MRI-PDFF and Transient Elastography: A European Multicenter Prospective Study.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is a growing concern in the aging population with human immunodeficiency virus (HIV). Screening for NAFLD is recommended in patients with metabolic risk factors or unexplained transaminitis. This study aimed to prospectively assess the prevalence and associated factors of liver steatosis and advanced fibrosis (AF) in HIV-monoinfected patients at risk of NAFLD. METHODS: We conducted a multicenter study in HIV-monoinfected patients, nonexcessive drinkers with metabolic syndrome, and/or persistently elevated liver enzymes, and/or clinical lipodystrophy. All participants had magnetic resonance imaging proton density fat fraction (MRI-PDFF), Fibroscan/controlled attenuation parameter (CAP), and cytokine and genetic analysis. RESULTS: From March 2014 to November 2015, we enrolled 442 participants and analyzed 402: male (85%); median age, 55 years (interquartile range [IQR], 50-61 years); body mass index, 27.0 kg/m2 (IQR, 23.6-28.7 kg/m2); metabolic syndrome (67%); and CD4 cell count, 630/mm3 (IQR, 510-832/mm3). Overall 257 of 402 (64%) had NAFLD (MRI-PDFF ≥5%). Among them, 11.3% had a liver stiffness ≥9.6 kPa, suggestive of AF. Multivariable analysis identified 7 factors of steatosis: high CD4-cell count (odds ratio [OR], 4.04; 95% confidence interval [CI], 1.92-8.51), high leptin level (OR, 2.12; 95% CI, 1.14-3.93), non-CC PNPLA3s738409 genetic polymorphism (OR, 1.92; 95% CI, 1.11-3.33), low high-density lipoprotein (OR, 1.83; 95% CI, 1.03-3.27), high triglycerides (OR, 1.48; 95% CI, 1.18-1.84), elevated alanine transaminase (OR, 1.23; 95% CI, 1.16-1.31), and hyper ferritinemia (OR, 1.05; 95% CI, 1.03-1.07). Two factors were associated with AF: high body mass index (OR, 1.23 ; 95% CI, 1.07-1.42 ; P = .005, and elevated aspartate aminotransferase (OR, 1.03; 95% CI, 1.01-1.05; P = .001). Using MRI-PDFF as a reference, CAP (best cutoff, 280 dB/m) had good accuracy (area under the receiver operating characteristic curve = 0.86; 95% CI, 0.82-0.90) for the diagnosis of moderate to severe steatosis. CONCLUSIONS: In a large cohort of HIV-moninfected patients at risk of NAFLD, steatosis is present in two-thirds of cases, and around 10% have AF. The CAP technique is accurate for screening steatosis in this population.

Evaluating the Impact of Peer Review on the Completeness of Reporting in Imaging Diagnostic Test Accuracy Research.

BACKGROUND: Despite the nearly ubiquitous reported use of peer review among reputable medical journals, there is limited evidence to support the use of peer review to improve the quality of biomedical research and in particular, imaging diagnostic test accuracy (DTA) research. PURPOSE: To evaluate whether peer review of DTA studies published by imaging journals is associated with changes in completeness of reporting, transparency for risk of bias assessment, and spin. STUDY TYPE: Retrospective cross-sectional study. STUDY SAMPLE: Cross-sectional study of articles published in Journal of Magnetic Resonance Imaging (JMRI), Canadian Association of Radiologists Journal (CARJ), and European Radiology (EuRad) before March 31, 2020. ASSESSMENT: Initial submitted and final versions of manuscripts were evaluated for completeness of reporting using the Standards for Reporting Diagnostic Accuracy Studies (STARD) 2015 and STARD for Abstracts guidelines, transparency of reporting for risk of bias assessment based on Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2), and actual and potential spin using modified published criteria. STATISTICAL TESTS: Two-tailed paired t-tests and paired Wilcoxon signed-rank tests were used for comparisons. A P value <0.05 was considered to be statistically significant. RESULTS: We included 84 diagnostic accuracy studies accepted by three journals between 2014 and 2020 (JMRI = 30, CARJ = 23, and EuRad = 31) of the 692 which were screened. Completeness of reporting according to STARD 2015 increased significantly between initial submissions and final accepted versions (average reported items: 16.67 vs. 17.47, change of 0.80 [95% confidence interval 0.25-1.17]). No significant difference was found for the reporting of STARD for Abstracts (5.28 vs. 5.25, change of -0.03 [-0.15 to 0.11], P = 0.74), QUADAS-2 (6.08 vs. 6.11, change of 0.03 [-1.00 to 0.50], P = 0.92), actual "spin" (2.36 vs. 2.40, change of 0.04 [0.00 to 1.00], P = 0.39) or potential "spin" (2.93 vs. 2.81, change of -0.12 [-1.00 to 0.00], P = 0.23) practices. CONCLUSION: Peer review is associated with a marginal improvement in completeness of reporting in published imaging DTA studies, but not with improvement in transparency for risk of bias assessment or reduction in spin. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 1.

Why did European Radiology reject my radiomic biomarker paper? How to correctly evaluate imaging biomarkers in a clinical setting.

This review explains in simple terms, accessible to the non-statistician, general principles regarding the correct research methods to develop and then evaluate imaging biomarkers in a clinical setting, including radiomic biomarkers. The distinction between diagnostic and prognostic biomarkers is made and emphasis placed on the need to assess clinical utility within the context of a multivariable model. Such models should not be restricted to imaging biomarkers and must include relevant disease and patient characteristics likely to be clinically useful. Biomarker utility is based on whether its addition to the basic clinical model improves diagnosis or prediction. Approaches to both model development and evaluation are explained and the need for adequate amounts of representative data stressed so as to avoid underpowering and overfitting. Advice is provided regarding how to report the research correctly. KEY POINTS: • Imaging biomarker research is common but methodological errors are encountered frequently that may mean the research is not clinically useful. • The clinical utility of imaging biomarkers is best assessed by their additive effect on multivariable models based on clinical factors known to be important. • The data used to develop such models should be sufficient for the number of variables investigated and the model should be evaluated, preferably using data unrelated to development.

Improved detection of subchondral erosions in the sacroiliac joints with T1-weighted fat-suppressed MRI.

OBJECTIVE: To compare the diagnostic performance of two different sets of magnetic resonance imaging (MRI) for the detection of subchondral erosions in the sacroiliac joints regarding the application of fat-water separation techniques when acquiring T1-weighted (T1w) images, using multi-detector computed tomography (MDCT) as the reference standard. METHODS: We retrospectively included 31 consecutive patients having or being suspected for axial spondyloarthritis (SpA) assessed using both MRI and MDCT. Three sets of images were independently assessed for the presence of erosions by two musculoskeletal radiologists (R1, R2): (1) MRI with standard T1w without fat suppression, (2) MRI with both T1w with and without fat suppression, and (3) MDCT. The diagnostic performance of both sets of MRIs was assessed using MDCT as the referent. RESULTS: The assessment of T1w images with fat suppression substantially increased sensitivity (76% vs. 63% R1; 70% vs. 60% R2), specificity (97% vs. 84% R1; 96% vs. 81% R2), positive predictive value (85% vs. 45% R1; 81% vs. 40% R2), and overall accuracy (94% vs. 80% R1; 92% vs. 77% R2) in the detection of erosions when compared to the assessment using T1w images without fat suppression. CONCLUSION: The assessment of T1w images with fat suppression substantially improves the diagnostic performance of MRI in the detection of erosions in the sacroiliac joints. KEY POINTS: • The presence of erosions in the sacroiliac joints may influence the decision on the diagnosis of axial spondyloarthritis. • T1w fat-suppressed MR imaging relatively increases the contrast between the joint space (high signal) and the adjacent subchondral bone (low signal), potentially improving the detection of erosions in the sacroiliac joints. • T1w fat-suppressed images improve the diagnostic performance of MRI in the detection of erosions in the sacroiliac joints compared to T1w without fat suppression, using MDCT as the reference.

Closing the gender gap in academic radiology: reasons for hope?

This Editorial Comment refers to the article by Bernard C. et al, Gender gap in articles published in European Radiology and CardioVascular and Interventional Radiology: evolution between 2002 and 2016, European Radiology, doi: 10.1007/s00330-019-06390-7.

MDCT arthrography assessment of scaphoid nonunion advanced collapse: distribution of cartilage damage and relationship with scaphoid nonunion features.

OBJECTIVES: Our primary aim was to evaluate the distribution and severity of cartilage damage in a sample of patients with scaphoid nonunion advanced collapse (SNAC), assessed on MDCT arthrography, with regard to two well-known SNAC staging systems. Secondarily, we wanted to see if the degree of cartilage damage varied with the location of the nonunion. METHODS: We retrospectively included 35 patients with a history of SNAC who had undergone MDCT arthrography. The location of the fracture was defined as the proximal, middle, or distal third of the scaphoid. Cartilage damage was assessed in 14 distinct regions of the wrist using a modified Whole-Organ Magnetic Resonance Imaging Score (WORMS) system. Staging of SNAC for each patient was based on the distribution of cartilage damage seen on MDCT arthrography. The one-way ANOVA test was used to evaluate whether global cartilage damage scores differed between patients with proximal vs middle and distal nonunion. RESULTS: The radial styloid-scaphoid (85.7%), the scaphoid-trapezium-trapezoid (60%), the scapho-capitate (57.1%), and the proximal radio-scaphoid joints (42.9%) were most commonly affected by degenerative cartilage damage. A substantial number of patients could not be classified according to the two SNAC staging systems. Patients with proximal nonunion exhibited a higher mean score of global cartilage damage than patients with middle or distal nonunion: 14.3 ± 9.5 (95% CI 9.8, 18.7) vs 8.6 ± 6.9 (95% CI 4.7, 12.4); p < 0.0001. CONCLUSION: The distribution of cartilage damage does not always follow the pattern of progressive osteoarthritis widely described in SNAC. Proximal scaphoid nonunion is related to greater severity of global cartilage damage.

Noncontrast Magnetic Resonance Lymphography.

BACKGROUND: Different imaging techniques have been used for the investigation of the lymphatic channels and lymph glands. Noncontrast magnetic resonance (MR) lymphography has significant advantages in comparison with other imaging modalities. METHODS: Noncontrast MR lymphography uses very heavily T2-weighted fast spin echo sequences which obtain a nearly complete signal loss in tissue background and specific display of lymphatic vessels with a long T2 relaxation time. The raw data can be processed with different algorithms such as maximum intensity projection algorithm to obtain an anatomic representation. RESULTS: Standard T2-weighted MR images easily demonstrate the location of edema. It appears as subcutaneous infiltration of soft tissue with a classical honeycomb pattern. True collection around the muscular area may be demonstrated in case of severe lymphedema. Lymph nodes may be normal in size, number, and signal intensity; in other cases, lymph nodes may be smaller in size or number of lymph nodes may be restricted. MR lymphography allows a classification of lymphedema in aplasia (no collecting vessels demonstrated); hypoplasia (a small number of lymphatic vessels), and numerical hyperplasia or hyperplasia (with an increased number of lymphatic vessels of greater and abnormal diameter). CONCLUSION: Noncontrast MR lymphography is a unique noninvasive imaging modality for the diagnosis of lymphedema. It can be used for positive diagnosis, differential diagnosis, and specific evaluation of lymphedema severity. It may also be used for follow-up evaluation after treatment.

Imaging-guided prognostic score-based approach to assess the benefits of combotherapy versus monotherapy with immune checkpoint inhibitors in metastatic MSI-H colorectal cancer patients.

BACKGROUND: This retrospective study determined survival responses to immune checkpoint inhibitors (ICIs), comparing mono- (mono) and combo-immunotherapy (combo) in patients with microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) by analyzing quantitative imaging data and clinical factors. METHODS: One hundred fifty patients were included from two centers and divided into training (n = 105) and validation (n = 45) cohorts. Radiologists manually annotated chest-abdomen-pelvis computed tomography and calculated tumor burden. Progression-free survival (PFS) was assessed, and variables were selected through Recursive Feature Elimination. Cutoff values were determined using maximally selected rank statistics to binarize features, forming a risk score with hazard ratio-derived weights. RESULTS: In total, 2258 lesions were annotated with excellent reproducibility. Key variables in the training cohort included: total tumor volume (cutoff: 73 cm3), lesion count (cutoff: 20), age (cutoff: 60) and the presence of peritoneal carcinomatosis. Their respective weights were 1.13, 0.96, 0.91, and 0.38, resulting in a risk score cutoff of 1.36. Low-score patients showed similar overall survival and PFS regardless of treatment, while those with a high-score had significantly worse survivals with mono vs combo (P = 0.004 and P = 0.0001). In the validation set, low-score patients exhibited no significant difference in overall survival and PFS with mono or combo. However, patients with a high-score had worse PFS with mono (P = 0.046). CONCLUSIONS: A score based on total tumor volume, lesion count, the presence of peritoneal carcinomatosis, and age can guide MSI-H mCRC treatment decisions, allowing oncologists to identify suitable candidates for mono and combo ICI therapies.

Relapse of Crohn's disease following ileal pouch-anal anastomosis: MDCT and MR features.

OBJECTIVE: The purpose of our study is to use MDCT and MR imaging to describe the normal ileal pouch and to identify features of Crohn's disease (CD) relapse in patients after ileal pouch-anal anastomosis (IPAA). CONCLUSIONS: After total colectomy followed by IPAA, features, optimally evaluated with pelvic MRI, such as fistulas, abscesses, pouch inflammation, and stenoses, indicate CD relapse. Although uncommon, radiologists should be aware that these imaging features strongly favor this diagnosis.

From Dose Reduction to Contrast Maximization: Can Deep Learning Amplify the Impact of Contrast Media on Brain Magnetic Resonance Image Quality? A Reader Study.

OBJECTIVES: The aim of this study was to evaluate a deep learning method designed to increase the contrast-to-noise ratio in contrast-enhanced gradient echo T1-weighted brain magnetic resonance imaging (MRI) acquisitions. The processed images are quantitatively evaluated in terms of lesion detection performance. MATERIALS AND METHODS: A total of 250 multiparametric brain MRIs, acquired between November 2019 and March 2021 at Gustave Roussy Cancer Campus (Villejuif, France), were considered for inclusion in this retrospective monocentric study. Independent training (107 cases; age, 55 ± 14 years; 58 women) and test (79 cases; age, 59 ± 14 years; 41 women) samples were defined. Patients had glioma, brain metastasis, meningioma, or no enhancing lesion. Gradient echo and turbo spin echo with variable flip angles postcontrast T1 sequences were acquired in all cases. For the cases that formed the training sample, "low-dose" postcontrast gradient echo T1 images using 0.025 mmol/kg injections of contrast agent were also acquired. A deep neural network was trained to synthetically enhance the low-dose T1 acquisitions, taking standard-dose T1 MRI as reference. Once trained, the contrast enhancement network was used to process the test gradient echo T1 images. A read was then performed by 2 experienced neuroradiologists to evaluate the original and processed T1 MRI sequences in terms of contrast enhancement and lesion detection performance, taking the turbo spin echo sequences as reference. RESULTS: The processed images were superior to the original gradient echo and reference turbo spin echo T1 sequences in terms of contrast-to-noise ratio (44.5 vs 9.1 and 16.8; P < 0.001), lesion-to-brain ratio (1.66 vs 1.31 and 1.44; P < 0.001), and contrast enhancement percentage (112.4% vs 85.6% and 92.2%; P < 0.001) for cases with enhancing lesions. The overall image quality of processed T1 was preferred by both readers (graded 3.4/4 on average vs 2.7/4; P < 0.001). Finally, the proposed processing improved the average sensitivity of gradient echo T1 MRI from 88% to 96% for lesions larger than 10 mm ( P = 0.008), whereas no difference was found in terms of the false detection rate (0.02 per case in both cases; P > 0.99). The same effect was observed when considering all lesions larger than 5 mm: sensitivity increased from 70% to 85% ( P < 0.001), whereas false detection rates remained similar (0.04 vs 0.06 per case; P = 0.48). With all lesions included regardless of their size, sensitivities were 59% and 75% for original and processed T1 images, respectively ( P < 0.001), and the corresponding false detection rates were 0.05 and 0.14 per case, respectively ( P = 0.06). CONCLUSION: The proposed deep learning method successfully amplified the beneficial effects of contrast agent injection on gradient echo T1 image quality, contrast level, and lesion detection performance. In particular, the sensitivity of the MRI sequence was improved by up to 16%, whereas the false detection rate remained similar.

Can Deep Learning Replace Gadolinium in Neuro-Oncology?: A Reader Study.

MATERIALS AND METHODS: This monocentric retrospective study leveraged 200 multiparametric brain MRIs acquired between November 2019 and February 2020 at Gustave Roussy Cancer Campus (Villejuif, France). A total of 145 patients were included: 107 formed the training sample (55 ± 14 years, 58 women) and 38 the separate test sample (62 ± 12 years, 22 women). Patients had glioma, brain metastases, meningioma, or no enhancing lesion. T1, T2-FLAIR, diffusion-weighted imaging, low-dose, and standard-dose postcontrast T1 sequences were acquired. A deep network was trained to process the precontrast and low-dose sequences to predict "virtual" surrogate images for contrast-enhanced T1. Once trained, the deep learning method was evaluated on the test sample. The discrepancies between the predicted virtual images and the standard-dose MRIs were qualitatively and quantitatively evaluated using both automated voxel-wise metrics and a reader study, where 2 radiologists graded image qualities and marked all visible enhancing lesions. RESULTS: The automated analysis of the test brain MRIs computed a structural similarity index of 87.1% ± 4.8% between the predicted virtual sequences and the reference contrast-enhanced T1 MRIs, a peak signal-to-noise ratio of 31.6 ± 2.0 dB, and an area under the curve of 96.4% ± 3.1%. At Youden's operating point, the voxel-wise sensitivity (SE) and specificity were 96.4% and 94.8%, respectively. The reader study found that virtual images were preferred to standard-dose MRI in terms of image quality (P = 0.008). A total of 91 reference lesions were identified in the 38 test T1 sequences enhanced with full dose of contrast agent. On average across readers, the brain lesion SE of the virtual images was 83% for lesions larger than 10 mm (n = 42), and the associated false detection rate was 0.08 lesion/patient. The corresponding positive predictive value of detected lesions was 92%, and the F1 score was 88%. Lesion detection performance, however, dropped when smaller lesions were included: average SE was 67% for lesions larger than 5 mm (n = 74), and 56% with all lesions included regardless of their size. The false detection rate remained below 0.50 lesion/patient in all cases, and the positive predictive value remained above 73%. The composite F1 score was 63% at worst. CONCLUSIONS: The proposed deep learning method for virtual contrast-enhanced T1 brain MRI prediction showed very high quantitative performance when evaluated with standard voxel-wise metrics. The reader study demonstrated that, for lesions larger than 10 mm, good detection performance could be maintained despite a 4-fold division in contrast agent usage, unveiling a promising avenue for reducing the gadolinium exposure of returning patients. Small lesions proved, however, difficult to handle for the deep network, showing that full-dose injections remain essential for accurate first-line diagnosis in neuro-oncology.

The diffusion-weighted imaging perfusion fraction f is a potential marker of sorafenib treatment in advanced hepatocellular carcinoma: a pilot study.

OBJECTIVE: To determine the total Apparent Diffusion Coefficient (ADC), the pure Diffusion coefficient (D) and the perfusion fraction (f) in advanced hepatocellular carcinoma (HCC) under sorafenib treatment. MATERIALS AND METHODS: Two target tumors were prospectively analyzed in 12 patients at baseline, 2-weeks and 2-months treatment using b values of 0, 200, 400, 800 s/mm. Repeatability error was estimated on a healthy volunteer. RESULTS: Lesion sizes, ADC and D values did not significantly change during treatment (overall mean values, respectively, 47.8 ± 31.0 mm, 1.34 ± 0.14 × 10⁻³ mm² s and 1.18 ± 0.22 × 10⁻³ mm²/s). However, f values significantly increased in seven responder patients (+38.39% at 2-weeks, +50.94% at 2-months, P = 0.005) while they decreased in five non responder patients (-41.93% at 2-weeks, P = 0.006). Furthermore, f was inversely correlated with αFP levels (P = 0.032) and responder patients had a higher mean overall survival (OS) than non responder patients (12.29 ± 4.46 vs. 7.80 ± 4.9 months). The % variation of f relative to baseline at 2-months was correlated with OS (P = 0.038) and symptomatic time to progression (P = 0.022). CONCLUSION: Contrary to ADC and D, the perfusion fraction f is a valuable marker of sorafenib treatment in advanced HCC.

CT and MRI features of ileostomies.

OBJECTIVE: The purpose of this article is to describe CT and MRI features of normal anatomy, variants, and pathologic conditions of different ileostomies. CONCLUSION: Multiplanar imaging techniques are useful to identify the complications related to stoma construction and preexisting disease. Understanding the indications for ileostomy construction, surgical techniques, and postoperative anatomy is important for differentiating normal and abnormal imaging features.

Letter to the Editor from Colle et al.

In their article, Fucà et al highlight that early tumor shrinkage and depth of response predict the prognosis of patients with metastatic colorectal cancer (mCRC) microsatellite instability (MSI-H)/deficient mismatch repair (dMMR) treated by immune checkpoint inhibitors (ICI). We are surprised that no cases of pseudoprogression (PSPD) were reported in their study. PSPDs were described under ICI in patients treated for MSI/dMMR mCRC. In a cohort of 123 patients treated with anti-PD1±antiCTL-4 for MSI/dMMR mCRC, we reported 12 patients with PSPD, representing 10% of the cohort. Of 12 patients with PSPD, 8 secondary achieved an objective response and were alive and free of progression at the data lock. Conversely, in Fucà's article, no PSDP was observed and the patients with primary radiological progression (21.7%) had a poor overall survival. These differences between the two series could be probably explained by the following points. First, Fucà et al use RECIST 1.1 criteria for radiological evaluation. Second, the first imaging was done after 8-9 weeks of treatment in Fucà's article, which may be late to detect PSPD. In conclusion, if the first evaluation is made during the first 3 months of treatment, using iRECIST criteria seems mandatory to avoid stopping treatment prematurely, especially in patients receiving anti-PD1 alone.

Pseudoprogression in patients treated with immune checkpoint inhibitors for microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer.

BACKGROUND: The efficacy of immune checkpoint inhibitors (ICIs) in microsatellite instability-high/DNA mismatch repair (MSI/dMMR) metastatic colorectal cancer (mCRC) is well established. ICIs are responsible for pseudoprogression (PSPD) that complicates clinical decisions. We evaluated the PSPD frequency in patients with MSI/dMMR mCRC treated with ICIs. PATIENTS AND METHODS: Consecutive patients with MSI/dMMR mCRC treated with ICIs from February 2015 to December 2019 at Saint-Antoine Hospital were included. Imaging was retrospectively and centrally reviewed according to Response Evaluation Criteria in Solid Tumours, version 1.1 (RECIST 1.1) and immune RECIST (iRECIST). PSPD was defined as an unconfirmed disease progression by iRECIST. RESULTS: One hundred twenty-three patients with MSI/dMMR mCRC were included. Thirty-six patients (29%) had radiological PD according to RECIST 1.1 during the median follow-up of 22.3 months (95% confidence interval [CI], 1.5-62.2), including 22 in the first 3 months (the primary radiological PD). Twenty-nine patients continued ICIs beyond PD. Twelve patients experienced PSPD, representing 10% of the population and 52% of the primary radiological PD. The median time to PSPD was 5.7 weeks (95% CI, 4.1-11.4). No PSPD was observed after 3 months. The PSPD incidence was 14.8% in patients treated with anti-PD1 alone (n = 9/61) and 4.8% in case of anti-PD1 plus anti-CTLA-4 (n = 3/62). Eight patients with PSPD experienced an objective response. The 2-year progression-free survival and overall survival rates for patients with PSPD were 70.0% (95% CI, 32.9-89.2) and 75.0% (95% CI, 29.8-93.4), respectively. CONCLUSION: Patients with MSI/dMMR mCRC treated with ICIs experienced PSPDs. PSPD occurred within the first 3 months and represented most of the primary radiological PDs. The use of iRECIST criteria should be questioned after 3 months.