Unenhanced T1 Research Articles

Intravesical local administration of pembrolizumab for treatment of bladder cancer: A novel strategy to minimize toxicity.

e14687 Background: A major hallmark of bladder cancer (BCa) is a higher treatment success rate than prostate cancer following stimulation of innate anti-tumor immune response either by intravesical BCG or to FDA approved intravenous anti-PD1 checkpoint antibody (pembrolizumab) approved for BCG resistant BCa since 2021. However, injected pembrolizumab is characterized by a markedly higher incidence (66%) of serious adverse events than the median duration of complete response of ~40% for non-muscle invasive BCa (NMIBC) and 15-20% for invasive BCa. Since the toxicity (fatigue, Pneumonitis and diarrhea) of injected pembrolizumab is linked to systemic breakdown of T-cell mediated immune surveillance we enquired whether analogous to BCG, pembrolizumab can be administered intravesically to safely induce a localized anti-tumor response in mouse model of BCa. Methods: Six weeks old female mice of B6D2F1 strain (n=10) were ad libitum fed carcinogen, N-butyl-N-4-hydroxybutyl nitrosamine (BBN) in drinking water (0.05% w/v) for 12 weeks. The presence of BBN evoked tumor was ascertained by unenhanced T2 weighted MRI at week 11 prior to single intravesical dosing by 24G transurethral catheter under isoflurane anesthesia of 0.1mL vehicle (sterile water) with or without 0.3mg of Pembrolizumab (Lipella Pharmaceuticals). 6 weeks later, T2 weighted MRI was repeated together with T1 mapping by ICE-MRI prior to organ harvest. Results: BBN feeding evoked multiclonal tumors (red*) of comparable size on T2 weighted MRI at week 11 but repeat MRI 7 weeks after treatment revealed that tumor progression and perivesical invasion noted in vehicle group was arrested in pembrolizumab group. Longest dimension of BBN tumor in vehicle treated mice was ≥ 1mm longer (p<0.05) than in pembrolizumab treated mice. T1 mapping revealed thickened bladder wall missed by T2 MRI. Conclusions: These findings on single intravesical dose of pembrolizumab (10mg/kg) in mice are consistent with human study on multiple intravesical dosing of BCG plus pembrolizumab (1-2mg/kg) in BCG resistant NMIBC patients. Intravesical pembrolizumab mirrors the limited systemic uptake of radiolabelled antibodies together with substantially higher ingress into tumor foci. The tumor selective ingress for BCa immunotherapy without any toxicity will be enhanced with Lipella Pharmaceutical’s liposomal delivery of Pembrolizumab.

Diagnostic accuracy of coronary artery stenosis and thrombosis assessment using unenhanced multiplanar 3D post-mortem cardiac magnetic resonance imaging

BackgroundA 3D sequence was introduced to unenhanced post-mortem cardiac magnetic resonance imaging (PMCMR) to enable multiplanar coronary artery image analysis and to investigate its diagnostic accuracy for the diagnosis of coronary artery stenosis and thrombosis. Materials and MethodsN = 200 forensic cases with suspected coronary artery pathology underwent 3 Tesla PMCMR (sequence used: T2 weighted transversal 3D turbo spin echo) before autopsy. Main coronary artery stenosis and thrombosis were assessed in PMCMR by multiplanar image analysis by two observers. Coronary artery histology was determined as the gold standard and compared to PMCMR. Sensitivity, specificity, negative (NPV) and positive predictive values (PPV) with 95% confidence intervals were calculated. ResultsFor all coronary arteries combined, sensitivity was 75% (PPV 73%) for the diagnosis of stenosis and 72% (PPV 71%) for the diagnosis of thrombosis. Specificity was 92% (NPV 90%) for correct diagnosis of non-existing stenosis and 97% (NPV 97%) for non-existing thrombosis. Sensitivity for correct diagnosis of different degrees of stenosis ranged between 67% and 80% (PPVs 67–82%); specificity ranged between 96% and 99% (NPVs 96–99%). ConclusionMultiplanar PMCMR coronary artery stenosis and thrombosis assessment based on an unenhanced T2 weighted 3D sequence provide moderate sensitivity and high specificity for the diagnosis of coronary artery stenosis and/or thrombosis. Hence, 3D T2w PMCMR cannot reliably detect existing coronary artery stenosis and thrombosis but may be particularly useful for the exclusion of stenosis or thrombosis of the main coronary arteries.

Correlation of histologic, imaging, and artificial intelligence features in NAFLD patients, derived from Gd-EOB-DTPA-enhanced MRI: a proof-of-concept study

ObjectiveTo compare unsupervised deep clustering (UDC) to fat fraction (FF) and relative liver enhancement (RLE) on Gd-EOB-DTPA-enhanced MRI to distinguish simple steatosis from non-alcoholic steatohepatitis (NASH), using histology as the gold standard.Materials and methodsA derivation group of 46 non-alcoholic fatty liver disease (NAFLD) patients underwent 3-T MRI. Histology assessed steatosis, inflammation, ballooning, and fibrosis. UDC was trained to group different texture patterns from MR data into 10 distinct clusters per sequence on unenhanced T1- and Gd-EOB-DTPA-enhanced T1-weighted hepatobiliary phase (T1-Gd-EOB-DTPA-HBP), then on T1 in- and opposed-phase images. RLE and FF were quantified on identical sequences. Differences of these parameters between NASH and simple steatosis were evaluated with χ2- and t-tests, respectively. Linear regression and Random Forest classifier were performed to identify associations between histological NAFLD features, RLE, FF, and UDC patterns, and then determine predictors able to distinguish simple steatosis from NASH. ROC curves assessed diagnostic performance of UDC, RLE, and FF. Finally, we tested these parameters on 30 validation cohorts.ResultsFor the derivation group, UDC-derived features from unenhanced and T1-Gd-EOB-DTPA-HBP, plus from T1 in- and opposed-phase, distinguished NASH from simple steatosis (p ≤ 0.001 and p = 0.02, respectively) with 85% and 80% accuracy, respectively, while RLE and FF distinguished NASH from simple steatosis (p ≤ 0.001 and p = 0.004, respectively), with 83% and 78% accuracy, respectively. On multivariate regression analysis, RLE and FF correlated only with fibrosis (p = 0.040) and steatosis (p ≤ 0.001), respectively. Conversely, UDC features, using Random Forest classifier predictors, correlated with all histologic NAFLD components. The validation group confirmed these results for both approaches.ConclusionUDC, RLE, and FF could independently separate NASH from simple steatosis. UDC may predict all histologic NAFLD components.Clinical relevance statementUsing gadoxetic acid–enhanced MR, fat fraction (FF > 5%) can diagnose NAFLD, and relative liver enhancement can distinguish NASH from simple steatosis. Adding AI may let us non-invasively estimate the histologic components, i.e., fat, ballooning, inflammation, and fibrosis, the latter the main prognosticator.Key Points• Unsupervised deep clustering (UDC) and MR-based parameters (FF and RLE) could independently distinguish simple steatosis from NASH in the derivation group.• On multivariate analysis, RLE could predict only fibrosis, and FF could predict only steatosis; however, UDC could predict all histologic NAFLD components in the derivation group.• The validation cohort confirmed the findings for the derivation group.

Using Machine Learning to Reduce the Need for Contrast Agents in Breast MRI through Synthetic Images.

Background Reducing the amount of contrast agent needed for contrast-enhanced breast MRI is desirable. Purpose To investigate if generative adversarial networks (GANs) can recover contrast-enhanced breast MRI scans from unenhanced images and virtual low-contrast-enhanced images. Materials and Methods In this retrospective study of breast MRI performed from January 2010 to December 2019, simulated low-contrast images were produced by adding virtual noise to the existing contrast-enhanced images. GANs were then trained to recover the contrast-enhanced images from the simulated low-contrast images (approach A) or from the unenhanced T1- and T2-weighted images (approach B). Two experienced radiologists were tasked with distinguishing between real and synthesized contrast-enhanced images using both approaches. Image appearance and conspicuity of enhancing lesions on the real versus synthesized contrast-enhanced images were independently compared and rated on a five-point Likert scale. P values were calculated by using bootstrapping. Results A total of 9751 breast MRI examinations from 5086 patients (mean age, 56 years ± 10 [SD]) were included. Readers who were blinded to the nature of the images could not distinguish real from synthetic contrast-enhanced images (average accuracy of differentiation: approach A, 52 of 100; approach B, 61 of 100). The test set included images with and without enhancing lesions (29 enhancing masses and 21 nonmass enhancement; 50 total). When readers who were not blinded compared the appearance of the real versus synthetic contrast-enhanced images side by side, approach A image ratings were significantly higher than those of approach B (mean rating, 4.6 ± 0.1 vs 3.0 ± 0.2; P < .001), with the noninferiority margin met by synthetic images from approach A (P < .001) but not B (P > .99). Conclusion Generative adversarial networks may be useful to enable breast MRI with reduced contrast agent dose. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Bahl in this issue.

MR imaging profile and histopathological characteristics of tumour vasculature, cell density and proliferation rate define two distinct growth patterns of human brain metastases from lung cancer

PurposeNon-invasive prediction of the tumour of origin giving rise to brain metastases (BMs) using MRI measurements obtained in radiological routine and elucidating the biological basis by matched histopathological analysis.MethodsPreoperative MRI and histological parameters of 95 BM patients (female, 50; mean age 59.6 ± 11.5 years) suffering from different primary tumours were retrospectively analysed. MR features were assessed by region of interest (ROI) measurements of signal intensities on unenhanced T1-, T2-, diffusion-weighted imaging and apparent diffusion coefficient (ADC) normalised to an internal reference ROI. Furthermore, we assessed BM size and oedema as well as cell density, proliferation rate, microvessel density and vessel area as histopathological parameters.ResultsApplying recursive partitioning conditional inference trees, only histopathological parameters could stratify the primary tumour entities. We identified two distinct BM growth patterns depending on their proliferative status: Ki67high BMs were larger (p = 0.02), showed less peritumoural oedema (p = 0.02) and showed a trend towards higher cell density (p = 0.05). Furthermore, Ki67high BMs were associated with higher DWI signals (p = 0.03) and reduced ADC values (p = 0.004). Vessel density was strongly reduced in Ki67high BM (p < 0.001). These features differentiated between lung cancer BM entities (p ≤ 0.03 for all features) with SCLCs representing predominantly the Ki67high group, while NSCLCs rather matching with Ki67low features.ConclusionInterpretable and easy to obtain MRI features may not be sufficient to predict directly the primary tumour entity of BM but seem to have the potential to aid differentiating high- and low-proliferative BMs, such as SCLC and NSCLC.

Correlation of semi-quantitative findings of endolymphatic hydrops in MRI with the audiometric findings in patients with Meniere's disease

Purpose: To investigate the correlation between vestibular hydrops (VH), cochlearhydrops (CH), vestibular aqueduct non-visibility (VANV), and visually increased perilymphatic enhancement (VIPE) with the findings of pure-tone audiometry (PTA) in Meniere’s disease (MD) patients.Methods: In this cross-sectional study, 53 ears belonging to 48 patients were divided into two groups and evaluated. In group “MD patients,” there were 24 ears of 19 patients diagnosed with the definite MD (14 patients with unilateral and 5 patients withbilateral involvements). The “control group” consisted of 29 non-symptomatic ears belonging to patients diagnosed with unilateral sudden sensory-neural hearing loss or unilateral schwannoma. All the patients underwent 2 sessions of temporal bone MRI using the same 3T system: an unenhanced axial T1, T2, and 3D-FLAIR MRI, an intravenous gadolinium-enhanced axial T1 fat-sat, and 4 h after the injection, an axial 3D-T2 cube and 3D-FLAIR session. VH, CH, VANV, and VIPE were assessed. Subsequently, the correlation between EH indices and PTA findings (in three frequency domains of low, middle, and high) were evaluated, and the predictive value of MRI was calculated.Results: VH was significantly correlated with the hearing threshold in the low, middle, and high-frequency domains. CH was also correlated with the hearing threshold in the low and middle domains. Contrarily, VIPE was not associated with hearing thresholds, and VANV was only correlated with the hearing threshold in low frequencies.Conclusion: The grade of VH, CH, and VANV were significantly correlated with the hearing thresholds in PTA.

Radiological evolution of autograft fat used for skull base reconstruction after transsphenoidal surgery for pituitary adenomas

PurposeCerebro-spinal fluid leak after transsphenoidal surgery for pituitary adenomas may be prevented by skull base reconstruction with fat autograft. However, graft changes may interfere with the interpretation of postoperative images. Our aim is to describe the radiological evolution of the fat autograft.MethodsA retrospective analysis was performed, including patients undergoing a transsphenoidal surgery for pituitary adenomas with a fat autograft for skull base reconstruction. Clinical and radiological data were collected, with assessment of fat autograft and extent of resection. Statistical analysis was performed using Kruskal–Wallis and Wilcoxon signed-rank test while Spearman’s Rho was used to analyze the relationship between variables.ResultsSeventy-two patients were included. Macroadenomas were diagnosed in 62 cases (86.1%) and in 21 cases an invasion of the cavernous sinus was described (29%). Gross total resection was achieved in 84.7% of cases. The volume of the fat graft significantly decreased between 3 months and 1 year after surgery (p = 0.01) and between 1 year and the last follow-up (mean 4.63 years, p < 0.01). Fat signal ratio significantly diminished between 3 months and 1 year in unenhanced and enhanced T1-weighted sequences (p = 0.04 and p = 0.02 respectively). Volume reduction was related to the decrease in signal ratio in unenhanced T1 sequences (p = 0.008).ConclusionFat resorbs with time: almost 50% of the fat volume is lost during the first year after surgery and 60% is resorbed at 4.6 years. T1-signal, before and after gadolinium injection, also decreases during the first year, probably because of the progressive fibrosis of the graft. This information will contribute to the interpretation of postoperative images.

Noninvasive assessment of clinically significant portal hypertension using ΔT1 of the liver and spleen and ECV of the spleen on routine Gd-EOB-DTPA liver MRI

PurposeTo analyze the predictive value of ΔT1 of the liver and spleen as well as the extracellular volume fraction (ECV) of the spleen as noninvasive biomarkers for the determination of clinically significant portal hypertension (CSPH) on routine Gd-EOB-DTPA liver MRI. Method195 consecutive patients with known or suspected chronic liver disease from 9/2018 to 7/2019 with Gd-EOB-DTPA liver MRI and abdominal T1 mapping were retrospectively included. Based on the presence of splenomegaly with thrombocytopenia, ascites and portosystemic collaterals, the patients were divided into noCSPH (n = 113), compensated CSPH (cCSPH, ≥1 finding without ascites; n = 55) and decompensated CSPH (dCSPH, ascites ± other findings; n = 27). T1 times were measured in the liver, spleen and abdominal aorta in the unenhanced and contrast-enhanced T1 maps. Native T1 times and ΔT1 of the liver and spleen as well as ECV of the spleen were compared between groups using the Kruskal-Wallis test with Dunn’s post hoc test. Furthermore, cutoff values for group differentiation were calculated using ROC analysis with Youden’s index. ResultsΔT1 of the liver was significantly lower in patients with cCSPH and dCSPH (p < 0.001) compared to patients with noCSPH. In the ROC analyses for differentiation between noCSPH and CSPH (cCSPH + dCSPH), a cutoff of < 0.67 for ΔT1 of the liver (AUC = 0.79) performed better than ΔT1 (AUC = 0.69) and ECV (AUC = 0.63) of the spleen with cutoffs of > 0.29 and > 41.9, respectively. ConclusionΔT1 of the liver and spleen in addition to ECV of the spleen allow for determination of CSPH on routine Gd-EOB-DTPA liver MRI.

T1 mapping for the diagnosis of early chronic pancreatitis: correlation with Cambridge classification system.

This study aims to determine if T1 relaxation time of the pancreas can detect parenchymal changes in early chronic pancreatitis (CP). This study retrospectively analyzed 42 patients grouped as no CP (Cambridge 0; n = 21), equivocal (Cambridge 1; n = 12) or mild CP (Cambridge 2; n = 9) based on magnetic resonance cholangiopancreatography findings using the Cambridge classification as the reference standard. Unenhanced T1 maps were acquired using a three-dimensional dual flip-angle gradient-echo technique on the same 1.5 T scanner with the same imaging parameters. There was no significant difference between the T1 relaxation times of Cambridge 0 and 1 group (p = 0.58). There was a significant difference (p = 0.0003) in the mean T1 relaxation times of the pancreas between the combined Cambridge 0 and 1 (mean = 639 msec, 95% CI: 617, 660) and Cambridge 2 groups (mean = 726 msec, 95% CI: 692, 759). There was significant difference (p = 0.0009) in the mean T1 relaxation times of the pancreas between the Cambridge 0 (mean = 636 msec, 95% CI: 606, 666) and Cambridge 2 groups (mean = 726 msec, 95% CI: 692,759) as well as between Cambridge 1 (mean = 643 msec, 95% CI: 608, 679) and Cambridge 2 groups (mean = 726 msec, 95% CI: 692,759) (p = 0.0017). Bland-Altman analysis showed measurements of one reader to be marginally higher than the other by 15.7 msec (2.4%, p = 0.04). T1 mapping is a practical method capable of quantitatively reflecting morphologic changes even in the early stages of chronic pancreatitis, and demonstrates promise for future implementation in routine clinical imaging protocols. T1 mapping can distinguish subtle parenchymal changes seen in early stage CP, and demonstrates promise for implementation in routine imaging protocols for the diagnosis of CP.

Clinico-pathological and follow-up analysis of 5 skeletal muscle single-organ vasculitis cases

Objectives: To delineate clinico-pathological features, treatment and outcome of skeletal muscle single-organ vasculitis (SM-SOV). Methods: The clinico-pathological characteristic of SM-SOV cases treated over 3 years in China-Japan Friendship Hospital were retrospectively analyzed and the data were compared with the cases from the literature. Results: Five patients (2 women and 3 men) with a median age of 36 years were included in this study. The main clinical manifestations were lower limb myalgia (5/5) and fever (1/5). The most frequent laboratory findings included high erythrocyte sedimentation rate (5/5), high C reactive protein (5/5) and leukocytosis (1/5). No elevated creatine kinase (CK) was found in these cases. Four patients received electromyogram examination and none of them showed myogenic injury. On MRI, hyperintense signals in T2 weighted image (T2WI) and/or short TI inversion recovery (STIR) and normal unenhanced T1 weighted image (T1WI) of one or several leg muscles was founded in all 5 patients. All muscle specimens showed nongranulomatous vasculitis without myonecrosis affecting small sized artery (5/5) in perimysia (75.0%, 3/4) or both perimysia and fascia (25.0%, 1/4). Corticosteroids (5/5) and immunosuppressants (5/5) were the main agents prescribed. With a median follow-up of 24 months, sustained remission was observed in 3 patients, relapses occurred in 2 patients. Conclusion: SM-SOV should be considered for patients with lower limb myalgia, high inflammatory markers and normal/low CK level. The diagnosis of SM-SOV should be applied when there are both histologic evidence of vasculitis and a minimum of 6 months of follow-up surveillance without evidences suggesting extra-muscular involvement. Corticosteroid combined with immunosuppressant is effective.

Evaluating the Relationship Between Dynamic Contrast-Enhanced MRI (DCE-MRI) Parameters and Pathological Characteristics in Breast Cancer.

Dynamic contrast-enhanced MRI (DCE-MRI) is used to evaluate tumor microvasculature. However, studies demonstrating an association between perfusion parameters derived from DCE-MRI and histopathologic characteristics are limited to a small set of histopathologic factors, and the results are inconsistent. To evaluate the relationship between DCE-MRI perfusion parameters and common histopathologic tumor characteristics used to predict angiogenesis and determine prognosis in breast cancer. Retrospective. In all, 105 breast cancer patients with invasive ductal carcinoma (122 lesions). 3.0T, turbo spin-echo (TSE) T1 -weighted, fat-suppressed T2 -weighted, TSE T2 -weighted, and dynamic unenhanced and contrast-enhanced 3D T1 high-resolution isotropic volume examination. One reviewer obtained perfusion parameters (Ktrans , kep , ve , and vp ) of each breast cancer from DCE MRI using the extended Tofts model with a fixed baseline T1 value and a population-based arterial input function. The relationship between DCE-MRI perfusion parameters and histopathologic tumor characteristics used to predict angiogenesis and determine prognosis was evaluated. Student's t-test, Mann-Whitney U-test, analysis of variance (ANOVA), and Kruskal-Wallis test were used. Triple-negative breast cancers exhibited higher Ktrans and kep than luminal cancers (P < 0.05). Estrogen receptor (ER)-negative tumors showed higher Ktrans than ER-positive tumors (P < 0.05). Progesterone receptor (PR)-negative tumors presented higher ve than PR-positive tumors (P < 0.05). Tumors with higher Ki-67 showed higher kep than tumors with lower Ki-67 (P < 0.05). P53-positive tumors exhibited higher Ktrans and kep than p53-negative tumors (P < 0.05). Higher histologic grade tumors (grade II/III) presented higher Ktrans , kep , vp (P < 0.05) than grade I tumors. Tumors with LVSI presented higher Ktrans and kep than tumors without LVSI (P < 0.05). Breast cancer presenting higher Ktrans and kep on DCE-MRI was associated with poor prognostic histopathologic factors. Therefore, pretreatment DCE-MRI perfusion parameters may be useful imaging biomarkers for the evaluation of tumor prognosis and angiogenesis. 3 TECHNICAL EFFICACY STAGE: 2.

Effect of Exposure to Gadodiamide and Brain Irradiation on T1 -Weighted Images and ADC Maps of the Dentate Nucleus.

Brain irradiation is considered a cofactor influencing the dentate nucleus (DN) signal intensity (SI) on unenhanced T1 -weighted images in patients exposed to gadolinium-based contrast agents (GBCAs). To assess the effect of gadodiamide and whole-brain radiation therapy (WBRT) on T1 -weighted images and on apparent diffusion coefficient (ADC) maps of DN. Single-center retrospective. In all, 125 patients who underwent brain MRIs were classified into four groups: 1) patients who did neither receive intravenous GBCAs injections nor irradiation (controls); 2) patients having ≥3 GBCAs-enhanced scans and no WBRT; 3) patients having WBRT and < 3 GBCAs-enhanced scans; and 4) patients having WBRT and ≥ 3 GBCAs-enhanced scans. 1.5T magnet, echo-planar diffusion weighted imaging (DWI) and unenhanced T1 -weighted sequences. The DN-to-pons SI ratio on unenhanced T1 -weighted images and ADC values of the DN were calculated. Values were compared between groups and relative to the cumulative gadolinium dose and to the time delay after WBRT. Statistical analysis included the Mann-Whitney U-test and Spearman's rank-order correlation. DN ADC values were not significantly different (P = 0.34) between patients exposed to gadodiamide (0.81 ± 0.06) and controls (0.83 ± 0.07). There were no differences in DN ADC values (P = 0.28) and DN-to-pons SI ratios (P = 0.42) between patients exposed to WBRT (ADC values: 0.85 ± 0.09; SI ratio: 1.11 ± 0.10) and controls (ADC values: 0.83 ± 0.06; SI ratio: 1.09 ± 0.06). There was a significant negative correlation between DN ADC values and the time (days) since the end of WBRT (r = - 0.33; 95% confidence interval [CI]: -0.55, -0.06; P < 0.05). We did not find changes suggestive of gadolinium-related tissue microstructural damage of the DN. The ADC values of the DN are associated with the time from WBRT. 3 TECHNICAL EFFICACY STAGE: 5.

Does Gadoterate Meglumine Cause Gadolinium Retention in the Brain of Children? A Case-Control Study.

Accumulation of macrocyclic gadolinium agents in children's brains remain to be determined. To demonstrate whether there is an intracranial macrocyclic gadolinium deposition after multiple contrast-enhanced MRI with gadoterate meglumine in a pediatric population. Retrospective case-control. In all, 45 children (age range: 5-17 years; mean, 13.7 ± 3.4 years) for the study group and 45 healthy children (age range: 5-17 years; mean, 13.7 ± 3.4 years) for the control group. T1 - and T2 -weighted axial images on a 1.5T scanner. Children with at least three enhanced brain MRIs and an age- and sex-matched control group with an unenhanced brain MRIs were compared in terms of T1 signal intensity (SI). All patients in the study group received gadoterate meglumine intravenously (0.1 mmol/kg). SI measurements were made by drawing six regions of interest (ROIs): dentate nuclei (DN), pons, globus pallidi (GP), frontal white matter (FWM), thalamus (T), clivus, and cerebrospinal fluid (CSF) for both groups on unenhanced T1 -weighted images. Student's t-test was used for comparison of SI. The Pearson correlation was calculated for the correlation between the SI and the number of gadolinium administrations. A significant difference was detected between two groups for DN/CSF, pons/CSF, GP/CSF, thalamus/CSF, and FWM/CSF (P < 0.001, P < 0.001, P = 0.002, P = 0.002, P = 0.024, respectively). There was no significant difference between the two groups for clivus/CSF (P = 0.15). A good correlation between the number of gadoterate meglumine administrations and the SI for DN/CSF, pons/CSF, GP/CSF, and T/CSF (r = 0.80, r = 0.73, r = 0.91, and r = 0.90, respectively) was found. A significant T1 SI increase reflecting gadolinium retention in the brain was detected for children with at least three gadoterate meglumine administrations in this series. The number of administrations correlated well with the increased SI. 3 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2020;51:1471-1477.

Assessment of apparent diffusion coefficient value as prognostic factor for renal cell carcinoma aggressiveness

BackgroundAssurance of prognostic elements is important for the management of renal cell carcinoma (RCC). Our goal was to check the relation between apparent diffusion coefficient (ADC) values and parameters predicting prognosis of RCC. Fifty pathologically confirmed RCC underwent diffusion-weighted (DW) MRI. ADC values were calculated using b factor (800 s/mm2). The correlation between ADC values and tumor size, cystic/necrotic feature, growth pattern, unenhanced T1, histological grade, clinical stage, and distant metastasis were analyzed.ResultsThe optimal ADC threshold for prognosis of RCC appeared to be 1.4 × 10−3 mm2/s. There was a significant inverse correlation between ADC values and growth pattern (R = − 0, P = 0.05), unenhanced T1(R = − 0.41, P = 0.01), cystic/necrotic feature (R = − 0.4, P = 0.01), histological grade (R = − 0.37, P = 0.02), clinical stage (r = − 0.4, P = 0.01), and distant metastasis (R = − 0.33, P = 0.04), and significant linear correlation with tumor size (R = 0.39, P < 0.02).ConclusionThe performance of ADC value as a newly proposed prognostic parameter follows with the degree of tumor differentiation and that may recognize extremely aggressive RCC. RCC with low ADC values should be inspected extensively for the risk of high pathological grade, high clinical stage, and distant metastasis.

Imaging biomarkers for malignant peripheral nerve sheath tumors in neurofibromatosis type 1.

To determine the utility of quantitative metrics obtained from fMRI using diffusion-weighted imaging (DWI)/apparent diffusion coefficient (ADC) mapping compared with metabolic (18F-fluorodeoxyglucose [FDG]-PET/CT) imaging in patients with neurofibromatosis type 1 (NF1) for the characterization of peripheral nerve sheath tumors (PNSTs) as benign or malignant. This Institutional Review Board-approved, Health Insurance Portability and Accountability Act-compliant study retrospectively reviewed imaging of 55 PNSTs in 21 patients with NF1. Imaging included anatomic (unenhanced T1, fluid-sensitive, contrast-enhanced T1-weighted), functional DWI (b = 50, 400, 800 s/mm2) and ADC mapping, magnetic resonance sequences, and FDG-PET/CT imaging. Anatomic (size), functional (minimum ADC values), and metabolic (maximum standardized uptake values [SUVmax]) imaging characteristics were recorded. ADC values were correlated with SUVmax. With histologic correlation for all malignant PNSTs (MPNSTs) or clinical or imaging stability (>12 months) for benign lesions used as reference standards, diagnostic accuracy was calculated. Of 55 PNSTs, there were 19 (35%) malignant and 36 (65%) benign PNSTs. Benign PNSTs were overall smaller than MPNSTs (largest diameter 4.3 ± 1.3 vs 8.2 ± 3.3 cm, respectively, p = 0.014). Benign PNSTs had higher ADCmin (×10-3 mm2/s) than MPNSTs (1.6 ± 0.4 vs 0.6 ± 0.2, respectively, p < 0.0001) and lower SUVmax than MPNSTs (3.2 ± 1.8 vs 8 ± 3.9, p < 0.0001, respectively). ADCmin correlated inversely with SUVmax (correlation coefficient r = -0.0.58, p < 0.0001). Maintaining a sensitivity of 100% with threshold values of ADCmin ≤1 or SUVmax >3.2, DWI yielded a specificity of 94% while FDG-PET/CT offered a specificity of 83%. Both quantitative metabolic imaging and functional imaging offer high sensitivity for the characterization of PNSTs in NF1; however, DWI/ADC mapping offers increased specificity and may be a more useful modality. This study provides Class II evidence that for patients with NF1, MRI using DWI/ADC mapping accurately distinguishes malignant and benign PNSTs.

Multiparametric MRI Evaluation of Complex Ovarian Masses

ObjectiveTo assess the role of diffusion-weighted imaging and dynamic contrast-enhanced magnetic resonance imaging in the categorization of complex ovarian masses into benign and malignant. Materials and MethodsThis prospective study was done on 33 complex ovarian masses. T1 and T2-weighted sequences, diffusion-weighted imaging, apparent diffusion coefficient, and dynamic contrast-enhanced magnetic resonance imaging were performed on 1.5 T MRI. Time-intensity curves, tissue signal intensity on unenhanced T1 images (SI0), maximum absolute contrast enhancement (SImax), time to reach SImax (Tmax), maximum relative SI (SIrel = [SImax − SI0]/SI0 ×100), maximum Slope (Slopemax = SIrel/Tmax ×100), and wash in rate (WIR = [SImax − SI0]/Tmax) were calculated. Histopathological diagnosis was taken as gold standard. ResultsA total of 20/33 masses were benign, 2/33 were borderline tumors, and 11/33 were malignant. Diffusion restriction was seen in all malignant masses and 13/20 benign masses. The mean apparent diffusion coefficient values showed a significant difference between malignant and benign, with 81.8% sensitivity and 63.6% specificity. Type III curve showed 100% specificity for malignant lesions. Tmax and Slopemax were useful in differentiating benign and malignant masses; with Tmax cut-off at 73.5 seconds having a high specificity (81.8%) and Slopemax cut-off at 0.83%/s having high sensitivity (91%) and negative predictive value (94.4%). ConclusionMultiparametric MRI confers high diagnostic accuracy in stratifying complex ovarian masses.

Switching from linear to macrocyclic gadolinium-based contrast agents halts the relative T1 -Weighted signal increase in deep gray matter of children with brain tumors: A retrospective study.

Studies have shown signal intensity (SI) changes in the brains of children exposed to repeated doses of a gadolinium-based contrast agent (GBCA). The trajectory of changes in relative dentate nucleus (DN) and globus pallidus (GP) SI in children receiving multiple doses of GBCA will alter when switched from linear to macrocyclic agents. Retrospective longitudinal. Thirty-five children, age range 0.5-17.0 years, undergoing brain tumor follow-up between 2006 and 2017. Unenhanced T1 WI, serial scans at both 1.5T and 3T. Regions of interest were drawn on DN, GP, and SIs normalized to middle cerebellar peduncle (DN/MCP) and cerebral white matter (GP/CWM), respectively. A change in SI ratios as a function of dose (slope gradient) calculated according to the type of contrast agent received: linear only, macrocyclic only, or switchover from linear to macrocyclic. For the latter, gradients were compared before and after switchover. The effect of anticancer treatment on slope gradient was tested. One-sample t-test or Mann-Whitney U-test for slope gradients differing from zero. Independent samples t-tests to compare slope gradient groups. Paired sample t-tests to compare slope gradients before and after switchover. A significant (P < 0.05) increase in SI ratio was observed following multiple doses of linear but not macrocyclic agents: mean percentage increase per dose in SI was 0.063% vs. -0.034% for DN/MCP, and 0.078% vs. 0.004% for GP/CWM ratios. A significant (P < 0.05) change of SI trajectory in the DN/MCP ratio was demonstrated when switching from a linear to macrocyclic agent. There was no difference in SI trajectory between patients who had anticancer therapies and those who did not, DN/MCP P = 0.740; GP/BWM P = 0.694. Switching from linear to macrocyclic gadolinium-based contrast agents seems to halt the relative T1 signal increase in deep gray matter in children. Anticancer treatments appeared to have no impact on the trajectory of T1 SI. 4 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;51:288-295.

Impact of nasopharyngeal irradiation and gadolinium administration on changes in T1 signal intensity of the dentate nucleus in nasopharyngeal malignancy patients without intracranial abnormalities.

Irradiation has been found to increase T1 signal intensity (SI) of the dentate nucleus (DN) by accelerating the gadolinium deposition in patients after multiple gadolinium-based contrast agent (GBCA) administrations. Several reports have focused on this phenomenon in patients with brain tumors; however, data in patients receiving irradiation with no intracranial abnormalities (NIAs) are lacking. To explore how nasopharyngeal irradiation affected SI changes on unenhanced T1 -weighted imaging (T1 WI) in the DN in nasopharyngeal malignancy (NPM) patients who presented with NIAs and who had multiple injection doses (IDs) of linear GBCAs. Single-center, retrospective, case-control study. In all, 132 subjects: 66 NPM patients, 66 matched controls. 1.5T and 3T/T1 WI, T2 WI, and fluid-attenuated inversion recovery (FLAIR). Radiation doses (RDs) were calculated by a radiotherapy technician. SIs were measured by a radiologist. The DN-to-cerebellar white matter (CWM) SI ratios and their relative percentage change (Rchange ) were compared. Shapiro-Wilk test, paired t-test, independent t-test, Mann-Whitney U-test, Pearson and Spearman correlation. DN/CWM b ratios or R change from the NPM group were significantly higher than those from the control group (P < 0.001). No significant difference of DN/CWM a ratios was found between the two groups (P > 0.05). Positive correlations between R change , DN/CWM b ratio, and the number of IDs were found in both the NPM and control groups (P < 0.01). The overall changes of DN/CWM b ratio or R change between NPM and control groups were higher for the higher-IDs subgroup (≥10) than for the lower-IDs subgroup (<10). Nasopharyngeal irradiation appeared to increase SI in T1 WI in NPM patients with NIAs and repeated GBCA administrations relative to control patients who also underwent GBCA administrations, especially when IDs ≥10. However, no significant association between R change and RDs to the DNs was found. 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:250-259.

Absence of dentate nucleus resting-state functional connectivity changes in nonneurological patients with gadolinium-related hyperintensity on T1 -weighted images.

The dentate nuclei of the cerebellum are the areas where gadolinium predominantly accumulates. It is not yet known whether gadolinium deposition affects brain functions. To assess whether gadolinium-dependent high signal intensity of the cerebellum on T1 -weighted images of nonneurological adult patients with Crohn's disease is associated with modifications of resting-state functional connectivity (RSFC) of the cerebellum and dentate nucleus. Observational, cross-sectional. Fifteen patients affected by Crohn's disease were compared with 16 healthy age- and gender-matched control subjects. All participants underwent neurological, neurocognitive-psychological assessment, and blood sampling. 1.5-T magnet blood oxygenation level-dependent (BOLD) functional MRI. High signal intensity on T1 -weighted images, cerebellum functional connectivity, neurocognitive performance, and blood circulating gadolinium levels. An unpaired two-sample t-test (age and sex were nuisance variables) was used to investigate between-group differences in cerebellar and dentate nucleus functional connectivity. Z-statistical images were set using clusters determined by Z > 2.3 and a familywise error (FWE)-corrected cluster significance threshold of P = 0.05. Dentate nuclei RSFC was not different (P = n.s.) between patients with gadolinium-dependent high signal intensity on T1 -weighted images and controls. Pre- and postcentral gyrus bilaterally and the right supplementary motor cortex showed a decrease of RSFC with the cerebellum hemispheres (P < 0.05 FWE-corrected) and was related to disease duration but not to gadodiamide cumulative doses (P = n.s.). Crohn's disease patients with gadolinium-dependent hyperintense dentate nuclei on unenhanced T1 -weighted images do not show dentate nucleus RSFC changes. 2 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2019;50:445-455.

Linear gadolinium-based contrast agent (gadodiamide and gadopentetate dimeglumine)-induced high signal intensity on unenhanced T1 -weighted images in pediatric patients.

Recent studies of adults have found an association between hyperintensity of the dentate nucleus (DN) and globus pallidus (GP) on T1 -weighted images (T1 WI) and a history of linear gadolinium-based contrast agent (GBCA) administration. Several reports have also focused on this phenomenon in pediatric patients; however, data in the current literature remains limited. To evaluate the associations between DN and GP T1 -signal increase and previous administration of linear GBCAs in pediatric patients. Single-center, retrospective, cross-sectional study. We included pediatric patients with histories of ≥5 linear GBCA (gadodiamide and gadopentetate dimeglumine) administrations (the "≥5 Linear GBCA administrations" group), 1-4 administrations (the "1-4 Linear GBCA administrations" group), and no history of GBCA administration (the "No GBCA administration" group). Each group included 42 patients. Therefore, 126 patients (male:female, 72:54; median age, 16 [range, 4-18] years) were included in this study. 1.5T/ Spin-echo unenhanced T1 -weighted imaging. Unenhanced T1 -weighted images were quantitatively analyzed by two radiologists. The DN-to-pons and GP-to-thalamus signal intensity ratios (DN-to-pons and GP-to-thalamus ratios, respectively) were compared. Wilcoxon test with the Bonferroni correction and intraclass correlation coefficients. The DN-to-pons ratio increased as the number of GBCA administrations increased (P < 0.0063). The GP-to-thalamus ratio of the "≥5 Linear GBCA administrations" group was significantly higher than those of the other two groups (P < 0.0001). The GP-to-thalamus ratio of the "1-4 Linear GBCA administrations" group did not differ significantly from that of the "No GBCA administration" group (P = 1.000). The DN-to-pons and GP-to-thalamus ratios' interobserver intraclass correlation coefficients were excellent (0.8236) and good (0.6738), respectively. High signal intensities in the DN and GP on T1 WI were associated with previous linear GBCA administration in pediatric patients. 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1046-1052.