Search

Introduction The molecular basis for the clinical heterogeneity observed in DLBCL was initially elucidated with gene expression profiling, identifying three distinct subgroups with prognostic relevance based on COO namely activated B-cell like (ABC), germinal center B-cell like (GCB) and a type 3 subtype. Shortly afterwards the Han's algorithm was developed allowing for widespread applicability and correlation of gene expression with protein expression. GCB profile at diagnosis is generally associated with superior long term outcomes compared to non-GCB in patients treated with conventional chemo-immunotherapy. Patients with relapsed/refractory disease (R/R) after front-line therapy undergo salvage treatment and, upon demonstration of objective response, proceed with high dose therapy and autologous transplantation (auto-HCT). Whether COO by Han's algorithm retains its prognostic significance post auto-HCT in patients with R/R DLBCL is not well established. Methods A retrospective analysis was carried out using the Mayo database across all three sites. It included all patients between 18-75 years of age who were diagnosed with de-novo DLBCL and underwent first auto-HCT for R/R disease. Patients must have received salvage treatment and shown chemotherapy sensitive disease. Patients with transformed DLBCL or other variants and those who underwent auto-HCT in first complete remission for high risk disease were excluded. Patients who had less than a partial response at time of transplantation and still underwent auto-HCT were also excluded. Primary endpoints included overall survival (OS); relapse and relapse-free survival (RFS). Continuous variables were summarized as mean (standard deviation) and median (range). Categorical variables were reported as frequency (percentage). Continuous baseline variables were compared between GCB and non-GCB using Wilcoxon rank sum test and categorical baseline variables were compared with Chi-squared test. Kaplan-Meier method was used to estimate 5 and 10-year rates of freedom from long-term events and draw corresponding survival curves. Multivariate Cox regression models were used to evaluate the impact of cell of origin on long-term survival after adjusting for baseline factors. All tests were two-sided with alpha level set at 0.05 for statistical significance. Results A total of 357 patients underwent auto-HCT between 2005 and 2018. Cell of origin was determined for 284 patients and these were included in the analysis. Median age was 61 (range: 19-78) years, and 64% patients were male. GCB and non-GCB patients did not differ significantly with regards to baseline factors (Table 1). During a median follow up of 1.7 years, 139 patients died, 151 had relapse and 175 either died or had relapse. Five year OS for GCB patients versus (vs) non-GCB was at 44% vs 64% (p=0.004) (Figure 1); relapse was at 67% vs 49% (p=0.012) and RFS was at 28% vs 50% (p=0.003). The difference between GCB and non-GCB groups remained statistically significant in multivariate analysis, with GCB patients 60% more likely to die and 50% more likely to experience relapse compared to non-GCB patients. The only other factor that retained significance in multivariate analysis for both endpoints was response at the time of transplant (Table 2A-C). Conclusions In this analysis, GCB DLBCL results in worse OS and higher relapse vs. non-GCB DLBCL following an auto-HCT. It is unclear if relapse/progression of GCB subtype after front-line therapy alters its natural history into a more aggressive disease. Disclosures Ansell: Trillium: Research Funding; ADC Therapeutics: Research Funding; Affimed: Research Funding; Bristol Myers Squibb: Research Funding; AI Therapeutics: Research Funding; Takeda: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding. Foran:Xencor: Research Funding; Trillium: Research Funding; Takeda: Research Funding; Kura Oncology: Research Funding; Aptose: Research Funding; Aprea: Research Funding; Actinium: Research Funding; Boehringer Ingelheim: Research Funding; Abbvie: Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Revolution Medicine: Consultancy; H3Biosciences: Research Funding; Agios: Honoraria, Research Funding. Tun:Celgene: Research Funding; Mundipharma: Research Funding; Curis: Research Funding; TG Therapeutics: Research Funding; Acrotech: Research Funding; DTRM Biopharma: Research Funding; Bristol-Myers Squibb: Research Funding. Kharfan-Dabaja:Daiichi Sankyo: Consultancy; Pharmacyclics: Consultancy.

Background: PCL is a rare and aggressive form of multiple myeloma (MM). It is associated with high risk cytogenetics, aggressive disease biology and a dismal prognosis. Dara has revolutionized the treatment of MM leading to deep and durable responses as a single agent and in combination with other agents. We evaluated the efficacy of Dara-based regimens in the treatment of PCL. Methods: Clinical charts of primary and secondary PCL patients treated at the Mayo Clinic Cancer Center between 2012-2019 were reviewed. Survival was analyzed with the Kaplan-Meier method. Plasma cell leukemia was defined by ≥5% peripheral blood plasma cells and/or absolute plasma cell count ≥0.5 x109/L (based on IMWG consensus statement).1 Results: Thirty-one patients were identified (55% female) with a median age at PCL diagnosis of 66 y (range 38-83). Fifteen (48%) had primary (p) PCL, while 14 (52%) had secondary (s) PCL. Nineteen (61%) had high risk cytogenetics with 11 (45%) del 17p, 4 (13%) t(14;16), 14 (45%) 1q amplification/duplication and 3(10%) t(4;14). Twelve (39%) had t(11;14). Eighteen (58%) patients had undergone autologous hematopoietic cell transplant (AHCT) with 12 (39%) having undergone AHCT following their diagnosis of PCL. Patients received a median of 2 prior lines of therapy (range 1-9) prior to receiving Dara-based regimens; 15 (42%) were refractory to an immunomodulatory agent (IMiD), 18 (58%) were refractory to a proteasome inhibitor (PI) and 10 (32%) were refractory to both. Twenty-eight (90%) were IMiD exposed, 31 (100%) were PI exposed. Eighteen (58%) were lenalidomide (R) refractory, 5(16%) were pomalidomide (P) refractory, 8 (26%) were carfilzomib (K) refractory and 13(42%) were bortezomib (V) refractory prior to receiving Dara. Four (13%) received Dara + chemotherapy, 8 (26%) received Dara + PI, 11 (35%) received Dara + IMiD, 5 (16%) received Dara + PI + IMiD and 4 (13%) received single agent Dara. Median follow up time was 26 months (m) (95% CI; 13-61) from diagnosis of PCL and 17m (95% CI; 10-23) from initiation of Dara. Overall response rate (ORR) to Dara-based regimens was 65% (20/31 ≥partial response). The median duration of response was 5.5m (95% CI; 5.6-12.7). The median time to first response was 1m (95% CI; 0.57-1.72) and the median time to best response was 1m (95% CI; 0.7-2.5). Since the start of Dara-based treatment, median progression free survival (PFS) was 4m (95% CI; 2-11, Figure 1A) and median overall survival (OS) was 9 m (95% CI; 5-21, Figure 1B). Patients with pPCL had superior PFS (19 m vs. 3m, p=0.0096) and OS (21 vs. 5m, p=0.0068, Figure 1C) following Dara-based treatment compared to those with sPCL, respectively. Being refractory to an IMiD, PI or both when receiving Dara did not affect PFS or OS. Patients with high risk cytogenetics had similar OS as compared to those with standard risk cytogenetics (8m vs.13m, p=0.89) following Dara-based treatment. After performing a landmark survival analysis at 3m, achieving ≥PR to a Dara-based regimen resulted in a trend towards superior OS (13m vs. 9 m, p=0.07, Figure 1D). Patients who underwent AHCT following the diagnosis of PCL had a superior OS (41m vs. 6m, p=0.020) however there were no PFS or OS differences whether Dara-based regimens were given before or after AHCT. Conclusions: Dara-based regimens induce a high ORR in patients with PCL with a rapid time to first response. However, the OS of patients with PCL, particularly sPCL remains dismal. Prospective trials for PCL patients using novel therapeutic strategies are warranted. 1Fernandez de Larrea, et al. Plasma Cell Leukemia: consensus statement on diagnostic requirements, response criteria, and treatment recommendations by the International Myeloma Working Group (IMWG). Leukemia. 2013; 27(4): 780-791. Disclosures Alhaj Moustafa: Acrotech: Consultancy. Kapoor:Janssen: Research Funding; Sanofi: Consultancy, Research Funding; Cellectar: Consultancy; Celgene: Honoraria; Amgen: Research Funding; Takeda: Honoraria, Research Funding; GlaxoSmithKline: Research Funding. Dingli:Millenium: Consultancy; Sanofi-Genzyme: Consultancy; Rigel: Consultancy; Bristol Myers Squibb: Research Funding; Karyopharm Therapeutics: Research Funding; Janssen: Consultancy; Alexion: Consultancy; Apellis: Consultancy. Ailawadhi:Phosplatin: Research Funding; Medimmune: Research Funding; BMS: Research Funding; Cellectar: Research Funding; Pharmacyclics: Research Funding; Janssen: Research Funding; Takeda: Honoraria; Amgen: Research Funding; Celgene: Honoraria.

Introduction: Response assessment at day 100 post Autologous Stem Cell Transplant (ASCT) is associated with long-term relapsed free survival (RFS) and overall survival (OS) in multiple myeloma (MM). The International Myeloma Working Group (IMWG) are the preferred criteria to define best response to treatment and define relapse. In the last years, response assessment has incorporated minimal residual disease (MRD) status -associated with improved RFS and OS (Munshi et al); and PET/CT combined with clinical characteristics -also associated with favorable outcomes (Zamagni et al. NCT01910987; MMY3033). The 2016 IMWG MRD criteria, combined imaging (PET/CT) plus next-generation sequencing (NGS) MRD-negative to define complete response (CR). To our knowledge, there is limited data examining the correlation and prognostic value of MRD and FDG-PET/CT at day 100 post ASCT in MM. IN this study, we aimed to determine the prognostic valued of MRD by NGS combined with PET/CT in RFS and OS status after high dose chemotherapy and ASCT in MM. Methods: Patients who underwent ASCT for MM at Mayo Clinic Arizona and had MRD and PET/CT data were included in the study. Clinical data was obtained via retrospective chart review. Cytogenetic risk (CyR) was classified using the mSMART criteria . Disease and ASCT related characteristics were compared by MRD status. MRD was measured by NGS on bone marrow aspirates using the previosly validated clonoSEQ ® Assay (Adaptive Biotechnologies Corporation, Seattle, USA) tracking the IgH, IgK and IgL rearrangements at a minimum sensitivity level of 10-5. MRD was defined by residual clonal cells per million nucleated cells as: negative= 0, borderline= 1-5, positive >5. PET/CT scans were performed locally at baseline and at day 100. Comparisons were performed using the chi-square test for categorical variables, Wilcoxon rank-sum test for continuos variables, McNemar's test and Cohens's Kappa for agreement measures. Results: A total of 103 patients had matched MRD and PET/CT assessment around day 100 (+/-9 days) and were included in the analysis. Median age at diagnosis was 62 years (range, 54-66 years), 71 patients (68.9%) were men. CyR was standard risk in 49 (47.6%), high-risk in 39 (37.9%) and unknown in 15 (14.6%) patients. Most 75 (72.8%) patients were MRD positive, 16 (15.5%) were MRD negative, and 12 (11.7%) borderline. The median main MRD clone detected was 64 (range 0-91,874). 70 patients (68%) and 33 (32%) had a negative and positive PET/CT respectively. The median follow-up time was 18 months (range, 13-31 months). At the time of data analysis, 10 patients (9.7%) had relapsed and only 4 (3.9%) had died. There was a high-correlation between MRD status and PET/CT, 31 patients (93.9%) with positive PET/CT were also MRD positive (p=0.0027). There were no statistical differences between PET/CT and CyR (p=0.95). We analyzed the correlation using the FREQ procedure (McNemars's test); there was a strong association between positive PET/CT and positive MRD in 31/33 patients (93.9%, high sensitivity), and low association for negative PET/CT the negative/borderline MRD in 26/70 (37.1%, low specificity; p Conclusions: In conclusion, we demonstrate that the combination of MRD by NGS (clonoSEQ ®) and PET/CT at day 100 are complementary and have a high sensitivity (true positive rate) and fair correlation of agreement but low specificity (true negative rate). PET/CT was the best most sensitive technique to prognosticate RFS and OS. We did not find prognostic correlation of MRD with RFS and OS. However, our findings might be confounded by the low risk of relapse and death, a longer follow-up may demonstrate clinically important differences. Our results add evidence that MRD plus PET/CT improve the definition of CR in MM patients post ASCT. Prospective studies are needed to elucidate the optimal timing and role of combined MRD, PET/CT with other prognostic markers of clinical outcomes. Disclosures Larsen: Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen Oncology: Honoraria, Membership on an entity's Board of Directors or advisory committees. Fonseca:Juno: Consultancy; Kite: Consultancy; Aduro: Consultancy; OncoTracker: Consultancy, Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy; Bayer: Consultancy; Janssen: Consultancy; Takeda: Consultancy; Novartis: Consultancy; Pharmacyclics: Consultancy; Sanofi: Consultancy; Oncopeptides: Consultancy; GSK: Consultancy; AbbVie: Consultancy; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy; BMS: Consultancy; Celgene: Consultancy.

Introduction: Daratumumab (D) is an anti-CD38 monoclonal antibody, used frequently in combination with immunomodulatory drugs (IMiDs), lenalidomide (Len) and pomalidomide (Pom). There are no studies comparing DRd to DPd in Len-exposed or refractory multiple myeloma (MM). We present the Mayo Clinic experience of DPd and DRd utilization and outcomes. Methods: We identified consecutive MM pts who received D, between 1/2015 and 4/2019 at Mayo Clinic. We included pts who were exposed (at least one full cycle, 21/28 days) or refractory (progression on full dose or maintenance Len during treatment or within 60 days of stopping Len) to Len prior to D and received 1 to 4 prior lines of therapy. Only Pts who received DRd and DPd were included. Results: Out of 411 evaluable pts 162 met the inclusion criteria; 67 were Len exposed, but not refractory and 95 were Len refractory. Pts' characteristics are shown in Table 1. DRd was used in 76 (47%) and DPd in 86 (53%) pts. Majority of pts (105; 65%) received DPd or DRd in the 2nd or 3rd line and 104 pts (64%) are still alive. In Len refractory pts, the median time from last dose of Len to D initiation was 1 mths (interquartile range 0-6.5). Seventy pts (43%) had high-risk cytogenetics (HR). Only 11 pts (7%) underwent autologous hematopoietic cell transplant after DPd or DRd regimen. There was no significant difference between pts who received DRd and DPd in terms of age (>65 years), gender, race, proportion exposed or refractory to Bortezomib, number of prior lines of treatment (>2), or HR status (p>0.05 for all). Pts who received DPd were 4 times more likely to be Len refractory compared to pts who received DRd, p=0.0008. Median follow up time for the whole cohort from initial diagnosis was 92 mths (CI 95%; 79.5-107), while from D start date was 30 mths (CI 95%; 27-34). Median PFS for the whole cohort was 21 mths (CI 95%; 15-25) and median OS was 138 mths (CI 95%; 111-193). In Len exposed but not refractory pts, n=67, the overall response rate (ORR) was 82% in the DRd group compared to 68% in the DPd group, p=0.2. There was no difference in median PFS; 25.5 mths (CI 95%; 23-NR) for DRd compared to 25 mths (CI 95%; 5-NR) for DPd, p=0.37. Similarly, there was no difference in median OS for DRd compared to DPd; NR mths (CI 95%; 138-NR) and 145.5 mths (CI 95%; 70-NR), respectively, p=0.06. In the 48 Len exposed but refractory pts who received DRd or DPd in 2nd or 3rd line, there was no difference in median PFS; 39 mths (CI 95%; 23-NR) for DRd compared to 21 mths (CI 95%; 3-NR) for DPd, p=0.11. Similarly, there was no difference in median OS for DRd compared to DPd; NR mths (CI 95%; NR-NR) and 145.5 mths (CI 95%; 36-NR), respectively, p=0.13. In Len refractory pts only, n=95, the ORR was 84% in the DRd group compared to 58% in the DPd group, p=0.009. There was no difference in median PFS; 25 mths (CI 95%; 13-32) for DRd compared to 9 mths (CI 95%; 5-15) for DPd, p=0.18. Similarly, there was no difference in median OS for DRd compared to DPd; 103 mths (CI 95%; 78-NR) and 106 mths (CI 95%; 66-183), respectively, p=0.5. In the 57 Len refractory pts who received DRd or DPd in 2nd or 3rd line, there was no difference in median PFS; 25 mths (CI 95%; 13-32) for DRd compared to 13 mths (CI 95%; 5-NR) for DPd, p=08. Similarly, there was no difference in median OS for DRd compared to DPd; 103 mths (CI 95%; 69-NR) and 105 mths (CI 95%; 47-NR), respectively, p=0.35. In the 16 Len exposed but not refractory pts with HR MM who received DRd or DPd in 2nd or 3rd line, the median PFS was better in the DRd group; 24.4 mths (CI 95%; 12-NR) compared to 3.3 mths (CI 95%; 1.9-27.5) for DPd, p=0.0093. However, there was no difference in median OS for DRd compared to DPd; NR mths (CI 95%; 51-NR) and NR mths (CI 95%; 18-NR), respectively, p=0.13. In the 29 Len refractory pts with HR MM who received DRd or DPd in 2nd or 3rd line, there was no statistically significant difference in median PFS; 18 mths (CI 95%; 6-43) for DRd compared to 6 mths (CI 95%; 4-13) for DPd, p=0.22.Similarly, there was no difference in median OS for DRd compared to DPd; 103 mths (CI 95%; 47-NR) and 53 mths (CI 95%; 26-105), respectively, p=0.2. Conclusions: D+IMiD regimens after prior Len exposure/refractoriness are commonly used in real-world, despite the lack of data from prospective clinical trials. Combining D with IMiDs in Len exposed or refractory pts is efficacious, whether the IMiD is Len or Pom. Our study shows that regardless of prior Len use, DRd is at least equivalent to DPd. Prospective studies should be done to confirm these observations. Disclosures Alhaj Moustafa: Acrotech: Consultancy. Larsen:Janssen Oncology: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kapoor:Janssen: Research Funding; GlaxoSmithKline: Research Funding; Cellectar: Consultancy; Celgene: Honoraria; Amgen: Research Funding; Takeda: Honoraria, Research Funding; Sanofi: Consultancy, Research Funding. Fonseca:Amgen: Consultancy; BMS: Consultancy; Celgene: Consultancy; Takeda: Consultancy; Bayer: Consultancy; Janssen: Consultancy; Novartis: Consultancy; Pharmacyclics: Consultancy; Sanofi: Consultancy; Merck: Consultancy; Juno: Consultancy; Kite: Consultancy; Aduro: Consultancy; OncoTracker: Consultancy, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Consultancy; GSK: Consultancy; AbbVie: Consultancy; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees. Dingli:Karyopharm Therapeutics: Research Funding; Rigel: Consultancy; Bristol Myers Squibb: Research Funding; Millenium: Consultancy; Sanofi-Genzyme: Consultancy; Janssen: Consultancy; Alexion: Consultancy; Apellis: Consultancy. Ailawadhi:Celgene: Honoraria; Amgen: Research Funding; Takeda: Honoraria; Janssen: Research Funding; Pharmacyclics: Research Funding; Cellectar: Research Funding; BMS: Research Funding; Medimmune: Research Funding; Phosplatin: Research Funding.

Purpose The role of neoadjuvant radiation for resectable pancreatic adenocarcinoma is controversial. We performed a prospective dose-escalation study of neoadjuvant stereotactic body radiation therapy (SBRT) with concurrent capecitabine and elective nodal irradiation (ENI) followed by surgical resection to explore the toxicity and feasibility of this approach. Methods and Materials Patients with biopsy proven, resectable cancers of the pancreatic head were enrolled. A 4 + 4 dose-escalation design was employed delivering 5 fractions of 5 to 7 Gy to primary tumor with concurrent capecitabine. The maximum tolerated dose level was expanded for an additional 4 patients. Patients at all dose levels were treated with ENI delivering 25 Gy in 5 fractions. Dose-limiting toxicity was defined as any grade ≥3 nonhematologic toxicity (National Cancer Institute Common Terminology Criteria for Adverse Events v4.0) attributable to chemoradiation occurring within 90 days of SBRT. Results A total of 17 patients were enrolled with 16 patients evaluable and 13 patients ultimately proceeding to surgery. The most common toxicity was nausea (56%). There were no dose-limiting toxicities, and SBRT was maximally dose escalated to 35 Gy in 5 fractions for 8 patients. All patients completing surgery had R0 resections. Seven patients (54%) had moderate treatment effect identified in pathologic specimens. Three patients (23%) developed locoregional recurrences, with 2 (15%) partially included within the treated volume. Conclusions SBRT was safely dose escalated to 35 Gy in 5 fractions along with concurrent capecitabine and ENI. This regimen will be used in a future expansion cohort.

To demonstrate the feasibility of combined delayed-phase gadoxetic acid (GA) and gadobenate dimeglumine (GD) enhanced liver MRI for improved detection of liver metastases, and to optimize contrast agent dose, timing, and flip angle (FA). Fourteen healthy volunteers underwent liver MRI at 3.0T at two visits during which they received two consecutive injections: 1. GA (Visit 1 = 0.025 mmol/kg; Visit 2 = 0.05 mmol/kg) and 2. GD (both visits = 0.1 mmol/kg) 20 min after GA administration. Two sub-studies were performed: Experiment-1 Eight subjects underwent multi-phase breath-held 3D-fat-saturated T1-weighted spoiled gradient echo (SGRE) imaging to determine the optimal imaging window for the combined GA + GD protocol to create a homogeneously hyperintense liver and vasculature (“plain-white-liver”) with maximum contrast to muscle which served as a surrogate for metastatic lesions in both experiments. Experiment-2 Six subjects underwent breath-held 3D-fat-saturated T1-weighted SGRE imaging at three different FA to determine the optimal FA for best image contrast. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were evaluated. Experiment-1 The combined GA + GD protocol created a homogeneously hyperintense liver and vasculature with maximum CNR liver/muscle at approximately 60–120 s after automatic GD-bolus detection. Experiment-2 Flip angles between 25° and 35° at a dose of 0.025 mmol/kg GA provided the best combination that minimized liver/vasculature CNR, while maximizing liver/muscle CNR. CNR performance to achieve a “plain-white-liver” was superior with 0.025 mmol/kg GA compared to 0.05 mmol/kg. Combined GA + GD enhanced T1-weighted MRI is feasible to achieve a homogeneously “plain-white-liver”. Future studies need to confirm that this protocol can improve sensitivity of liver lesion detection in patients with metastatic liver disease.

PURPOSE: This study compares splenic proton density fat fraction (PDFF) measured using confounder-corrected chemical-shift-encoded (CSE) MRI to MR spectroscopy in human patients at 3T. METHODS: This was a prospectively designed ancillary study to various previously described single-center studies performed in adults and children with known or suspected nonalcoholic fatty liver disease. Patients underwent magnitude-based MRI (MRI-M), complex-based MRI (MRI-C), high signal-to-noise variants (Hi-SNR MRI-M and Hi-SNR MRI-C), and MR spectroscopy (MRS) at 3T for spleen PDFF estimation. PDFF from CSE-MRI methods were compared to MRS-PDFF using Wilcoxon signed-rank tests. Demographics were summarized descriptively. Spearman’s rank correlations were computed pairwise between CSE-MRI methods. Individual patient measurements were plotted for qualitative assessment. A significance level of 0.05 was used. RESULTS: Forty-seven patients (20 female, 27 male) including 12 adults (median: 55 years old) and 35 children (median: 12 years old). Median PDFF estimated by MRS, MRI-M, Hi-SNR-MRI-M, MRI-C, and Hi-SNR-MRI-C was 1.0%, 2.3%, 1.9%, 2.2%, and 2.0%. The four CSE-MRI methods estimated statistically significant higher spleen PDFF values compared to MRS (p < 0.0001 for all). Pairwise associations in spleen PDFF values measured by different CSE-MRI methods were weak, with the highest Spearman’s rank correlations being 0.295 between MRI-M and Hi-SNR-MRI-M; none were significant after correction for multiple comparisons. No qualitative relationship was observed between PDFF measurements among the various methods. CONCLUSION: Overestimation of PDFF by CSE-MRI compared to MRS and poor agreement between related CSE-MRI methods suggest that non-zero PDFF values in human spleen are artifactual.

Ferumoxytol is a superparamagnetic iron oxide nanoparticle used off-label as an intravascular magnetic resonance imaging (MRI) contrast agent. Additionally, ferumoxytol-uptake by macrophages facilitates detection of inflammatory sites by MRI through ferumoxytol-induced image contrast changes. Therefore, ferumoxytol-enhanced MRI holds great potential for assessing vascular function and inflammatory response, critical to determine placental health in pregnancy. This study sought to assess the fetoplacental unit and selected maternal tissues, pregnancy outcomes, and fetal well-being after ferumoxytol administration. In initial developmental studies, seven pregnant rhesus macaques were imaged with or without ferumoxytol administration. Pregnancies went to term with vaginal delivery and infants showed normal growth rates compared to control animals born the same year that did not undergo MRI. To determine the impact of ferumoxytol on the maternal–fetal interface (MFI), fetal well-being, and pregnancy outcome, four pregnant rhesus macaques at ∼100 gestational day underwent MRI before and after ferumoxytol administration. Collection of the fetoplacental unit and selected maternal tissues was performed 2–3 days following ferumoxytol administration. A control group that did not receive ferumoxytol or MRI was used for comparison. Iron levels in fetal and MFI tissues did not differ between groups, and there was no significant difference in tissue histopathology with or without exposure to ferumoxytol, and no effect on placental hormone secretion. Together, these results suggest that the use of ferumoxytol and MRI in pregnant rhesus macaques does not negatively impact the MFI and can be a valuable experimental tool in research with this important animal model.Summary SentenceFerumoxytol magnetic resonance imaging for non-invasive pregnancy monitoring of the rhesus macaque does not impact histopathology or iron content of the maternal–fetal interface.

OBJECTIVES: To assess the feasibility of ferumoxytol-enhanced MRI in pregnancy with a nonhuman primate model. MATERIALS AND METHODS: In this prospective study, eleven pregnant rhesus macaques at day 98 ± 5 of gestation were divided into three groups, untreated control (UC) (n = 3), saline control (SC) (n = 4) and interleukin 1 beta (IL-1β) treated (IT) (n = 4), which were administered with either saline or IL-1β into the amniotic fluid. All animals were imaged at multiple time points before and after ferumoxytol administration (4 mg/kg). Longitudinal R2* and susceptibility of tissues were obtained using region-of-interest analysis and the longitudinal changes were assessed using linear mixed models and Student’s t-test. RESULTS: In fetuses, a slope of 0.3s(−1)/day (P = 0.008), 0.00ppm/day (P = 0.699) and −0.2s(−1)/day (P = 0.023) was observed in liver R2*, liver susceptibility, and lung R2*, respectively. In placentas, R2* and susceptibility increased immediately after ferumoxytol administration (P < 0.001) and decreased to baseline within two days. The mean change from baseline showed no significant difference between the SC group and the IT group at all scan time points. In maternal livers, R2* increased immediately after ferumoxytol administration, further increased at one-day, and then decreased but remained elevated (P < 0.001). The mean change from baseline showed no significant difference between the SC group and the IT group at all scan time points. CONCLUSIONS: This work demonstrates the feasibility of quantitative ferumoxytol-enhanced MRI to measure dynamics of ferumoxytol delivery and washout in the placenta. Stable MRI measurements indicated no evidence of iron deposition in fetal tissues of nonhuman primates after maternal ferumoxytol exposure.

Purpose Determine the impact of the microscopic spatial distribution of iron on relaxometry and susceptibility-based estimates of iron concentration. Methods Monte Carlo simulations and in vitro experiments of erythrocytes were used to create different microscopic distributions of iron. Measuring iron with intact erythrocyte cells created a heterogeneous distribution of iron, whereas lysing erythrocytes was used to create a homogeneous distribution of iron. Multi-echo spin echo and spoiled gradient echo acquisitions were then used to estimate relaxation parameters ( R 2 and R 2 * ) and susceptibility. Results Simulations demonstrate that R 2 and R 2 * measurements depend on the spatial distribution of iron even for the same iron concentration and volume susceptibility. Similarly, in vitro experiments demonstrate that R 2 and R 2 * measurements depend on the microscopic spatial distribution of iron whereas the quantitative susceptibility mapping (QSM) susceptibility estimates reflect iron concentration without sensitivity to spatial distribution. Conclusions R 2 and R 2 * for iron quantification depend on the spatial distribution or iron. QSM-based estimation of iron concentration is insensitive to the microscopic spatial distribution of iron, potentially providing a distribution independent measure of iron concentration.

Ferumoxytol is a superparamagnetic iron oxide nanoparticle (SPION) used off-label as an intravascular magnetic resonance imaging (MRI) contrast agent. Additionally, ferumoxytol-uptake by macrophages facilitates detection of inflammatory sites by MRI through ferumoxytol-induced image contrast changes. Therefore, ferumoxytol-enhanced MRI holds great potential for assessing vascular function and inflammatory response, critical to determine placental health in pregnancy. This study sought to assess the fetoplacental unit and selected maternal tissues, pregnancy outcomes, and fetal well-being after ferumoxytol administration. In initial developmental studies, pregnant rhesus macaques were imaged with and without ferumoxytol administration. Pregnancies went to term with vaginal delivery and infants showed normal growth rates compared to control animals born the same year that did not undergo MRI. To determine the impact of ferumoxytol on the maternal-fetal interface, fetal well-being, and pregnancy outcome, four pregnant rhesus macaques at ∼100 gd (gestational day) underwent MRI before and after ferumoxytol administration. Collection of the fetoplacental unit and selected maternal tissues was performed 3-4 days following ferumoxytol administration. A control group that did not receive ferumoxytol or MRI was used for comparison. Iron levels in fetal and maternal-fetal interface tissues did not vary between groups. There was no significant difference in tissue histopathology with or without exposure to ferumoxytol, and no effect on placental hormone secretion. Together, these results suggest that the use of ferumoxytol and MRI in pregnant rhesus macaques will not introduce a detectable risk to the mother or fetus at the time of imaging or up to one year following normal vaginal delivery.Summary SentenceFerumoxytol magnetic resonance imaging for non-invasive pregnancy monitoring of the rhesus macaque does not impact histopathology or iron content of the maternal-fetal interface.

PURPOSE Recent studies have suggested the presence of short-T2 * signals in the liver, which may confound chemical shift-encoded (CSE) fat quantification when using short echo times (TEs). The purpose of this study was to characterize the liver signal at short echo times and to determine its impact on liver fat quantification. METHODS An ultrashort echo time (UTE) chemical shift-encoded MRI (CSE-MRI) technique and a multicomponent reconstruction were developed to characterize short-T2 * liver signals. Subsequently, liver fat fraction was quantified using a short-TE (first TE = 0.7 ms) and UTE CSE-MRI acquisitions and compared with a standard CSE-MRI (first TE = 1.2 ms). RESULTS Short-T2 * signals were consistently observed in the liver of all healthy volunteers imaged at both 1.5T and 3.0T. At 3.0T, short-T2 * signal fractions of 9.6 ± 1.5%, 7.0 ± 1.7%, and 7.4 ± 1.7% with T2 * of 0.23 ± 0.05 ms, 0.20 ± 0.05 ms, and 0.10 ± 0.02 ms were measured in healthy volunteers, patients with liver cirrhotic disease, and patients with hepatic steatosis (but no cirrhosis), respectively. For proton density fat fraction (PDFF) estimation, 1.7% (P < .01) and 3.4% (P < .01) biases were observed in subjects imaged using short-TE CSE-MRI and using UTE CSE-MRI at 1.5T, respectively. The biases were reduced to 0.4% and -0.7%, respectively, by excluding short echoes less than 1 ms. A 3.2% bias (P < .01) was observed in subjects imaged using UTE CSE-MRI at 3.0T, which was reduced to 0.1% by excluding short echoes

The need for a guidance document on MR safe practices arose from a growing awareness of the MR environment's potential risks and adverse event reports involving patients, equipment, and personnel. Initially published in 2002, the American College of Radiology White Paper on MR Safety established de facto industry standards for safe and responsible practices in clinical and research MR environments. The most recent version addresses new sources of risk of adverse events, increases awareness of dynamic MR environments, and recommends that those responsible for MR medical director safety undergo annual MR safety training. With regular updates to these guidelines, the latest MR safety concerns can be accounted for to ensure a safer MR environment where dangers are minimized. Level of Evidence: 1 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2020;51:331-338.

PURPOSE: To longitudinally monitor liver fat before and after bariatric surgery by using quantitative chemical shift-encoded (CSE) MRI and to compare with changes in body mass index (BMI), weight, and waist circumference (WC). MATERIALS AND METHODS: For this prospective study, which was approved by the internal review board, a total of 126 participants with obesity who were undergoing evaluation for bariatric surgery with preoperative very low calorie diet (VLCD) were recruited from June 27, 2010, through May 5, 2015. Written informed consent was obtained from all participants. Participants underwent CSE MRI measuring liver proton density fat fraction (PDFF) before VLCD (2–3 weeks before surgery), after VLCD (1–3 days before surgery), and 1, 3, and 6–10 months following surgery. Linear regression was used to estimate rates of change of PDFF (ΔPDFF) and body anthropometrics. Initial PDFF (PDFF(0)), initial anthropometrics, and anthropometric rates of change were evaluated as predictors of ΔPDFF. Mixed-effects regression was used to estimate time to normalization of PDFF. RESULTS: Fifty participants (mean age, 51.0 years; age range, 27–70 years), including 43 women (mean age, 50.8 years; age range, 27–70 years) and seven men (mean age, 51.7 years; age range, 36–62 years), with mean PDFF(0) ± standard deviation of 18.1% ± 8.6 and mean BMI(0) of 44.9 kg/m(2) ± 6.5 completed the study. By 6–10 months following surgery, mean PDFF decreased to 4.9% ± 3.4 and mean BMI decreased to 34.5 kg/m(2) ± 5.4. Mean estimated time to PDFF normalization was 22.5 weeks ± 11.5. PDFF(0) was the only strong predictor for both ΔPDFF and time to PDFF normalization. No body anthropometric correlated with either outcome. CONCLUSION: Average liver proton density fat fraction (PDFF) decreased to normal (< 5%) by 6–10 months following surgery, with mean time to normalization of approximately 5 months. Initial PDFF was a strong predictor of both rate of change of PDFF and time to normalization. Body anthropometrics did not predict either outcome. Online supplemental material is available for this article. © RSNA, 2018

The purpose of this review article is to acquaint the reader with the current state of the art for the noncardiovascular imaging biomarkers of metabolic syndrome found on noncontrast computed tomography (NCCT) of the chest and their prognostic significance. Routine chest NCCT includes quantitative information with regard to tissue density and organ volumes in the neck, chest, and upper abdomen. The specific imaging biomarkers that may be seen in association with metabolic syndrome include low thyroid iodine organification, hepatic steatosis, sarcopenia (muscle volume and density), demineralization of the thoracic and upper lumbar vertebral bodies, loss of axial skeletal muscle mass, premature lung inflammation, and an increased deposition of subcutaneous and visceral fat. These easily identified imaging biomarkers can have prognostic implications, which include nonalcoholic steatohepatitis, cirrhosis, hypothyroidism, early lung fibrosis with interstitial abnormalities, sarcopenia, and osteoporotic thoracic and lumbar spine vertebral body compression fractures. NCCT examinations of the chest have the opportunity to become an important imaging tool for outcomes research.

7530 Background: Clinical trials of novel salvage therapies (ST) have encouraging outcomes for relapsed/refractory classic Hodgkin lymphoma (R/R cHL) eligible for autologous stem cell transplant (ASCT). In this observational study, we report efficacies and outcomes of different ST in ASCT-eligible R/R cHL. Methods: Consecutive ASCT-eligible R/R cHL pts at 3 Mayo Clinic sites were included. Demographics and clinical variables at relapse were recorded by medical records review. Time to event endpoints were defined from relapse. Univariate associations were confirmed in multivariate models of age, sex, B symptoms, stage, bulky disease (BD, single mass > 6 cm) extra nodal disease (END), primary refractory disease (PRD) and early relapse (ER, within 1 year). Results: From Jan 2008 to May 2020, 207 ASCT-eligible pts with R/R cHL were included. Median age was 33 (24-43) years, 53% were male, 52% had advanced stage, 24% had BD, 36% had B symptoms, 41% had END, 11% had PRD and 43% had ER. All patients received ST and underwent ASCT; 43 (21%) received 2 ST, 14 (7%) 3 ST and 4 (0.5%) received 4 ST. 6 groups of ST were identified: ifosfamide, carboplatin and etoposide (ICE), bendamustine/brentuximab (BBV), brentuximab vedotin (BV), gemcitabine-based therapy (Gem), checkpoint inhibitor (CPI), and others. Table lists response to first line ST. BBV had significantly higher overall response rate (ORR) and complete response (CR) as first ST in univariate and multivariate models. 114 (79%) after ICE, 30 (97%) after BBV, 15 (56%) after BV, 25 (76%) after Gem, 8 (73%) after CPI and 15 (79%) after other ST underwent ASCT. Higher number of pts were bridged to ASCT after BBV than ICE (p95 0.2-0.8)) and higher number of ST was associated with lower OS (HR 2 (CI95 1.4-3)) in multivariate model (p95 1.2-3.5), p

Proteasome inhibitors have become an integral part of myeloma therapy. Considerable efforts have gone into optimizing this therapeutic approach to obtain maximal proteasome inhibition with least toxicity. Ixazomib is the first oral proteasome inhibitor to enter the clinic and has been studied as a single agent as well as in various combinations. The current trial was designed to examine the efficacy and toxicity of combining 2 different doses of ixazomib (4 mg and 5.5 mg given weekly for 3 of 4 weeks) with 40 mg weekly of dexamethasone, in relapsed myeloma. Seventy patients were enrolled, 35 patients randomly assigned to each ixazomib dose. Overall, 30 (43%; 95% confidence interval, 31-55) of the patients achieved a confirmed partial response or better, with 31% achieving a response with 4 mg and 54% with 5.5 mg of ixazomib. The median event-free survival (EFS) for the entire study population was 8.4 months; 1-year overall survival was 96%. The EFS was 5.7 months for patients with prior bortezomib exposure and 11.0 months for bortezomib-naïve patients. A grade 3 or 4 adverse event considered at least possibly related to treatment was seen in 11 (32%) patients at 4 mg and in 21 (60%) at 5.5 mg. Dose reductions were more frequent with 5.5 mg dose. Overall, the ixazomib with dexamethasone has good efficacy in relapsed myeloma, is well-tolerated and with higher response rate at 5.5 mg, albeit with more toxicity. This study was registered at www.clinicaltrials.gov as #NCT01415882.

Purpose The purpose of this work was to characterize the effects of concomitant gradients (CGs) on chemical shift encoded (CSE)-based estimation of B0 field map, proton density fat fraction (PDFF), and R2*. Theory A theoretical framework was used to determine the effects of CG-induced phase errors on CSE-MRI data. Methods Simulations, phantom experiments, and in vivo experiments were conducted at 3 Tesla to assess the effects of CGs on quantitative CSE-MRI techniques. Correction of phase errors attributable to CGs was also investigated to determine whether these effects could be removed. Results Phase errors attributed to CGs introduce errors in the estimation of B0 field map, PDFF, and R2*. Phantom and in vivo experiments demonstrated that CGs can introduce estimation errors greater than 30 Hz in the B0 field map, 10% in PDFF, and 16 s−1 in R2*, 16 cm off isocenter. However, CG phase correction before parameter estimation was able to reduce estimation errors to less than 10 Hz in the B0 field map, 1% in PDFF, and 2 s−1 in R2*. Conclusion CG effects can impact CSE-MRI, leading to inaccurate estimation of B0 field map, PDFF, and R2*. However, correction for phase errors caused by CGs improve the accuracy of quantitative parameters estimated from CSE-MRI acquisitions. Magn Reson Med, 2016. © 2016 International Society for Magnetic Resonance in Medicine

To quantify the trends in imaging use for the diagnosis of appendicitis.A retrospective study covering a 22-year period was conducted at an academic medical center. Patients were identified by International Classification of Diseases-9 diagnosis code for appendicitis. Medical record data extraction of these patients included imaging test used (ultrasound, CT, or MRI), gender, age, and body mass index (BMI). The proportion of patients undergoing each scan was calculated by year. Regression analysis was performed to determine whether age, gender, or BMI affected imaging choice.The study included a total of 2,108 patients, including 967 (43.5%) females and 599 (27%) children (18 years old). CT use increased over time for the entire cohort (2.9% to 82.4%, P.0001), and each subgroup (males, females, adults, children; P.0001 for each). CT use increased more in females and adults than in males and children, but differences in trends were not statistically significant (male versus female, P = .8; adult versus child, P = .1). The percentage of patients who had no imaging used for the diagnosis of appendicitis decreased over time (P.0001 overall and for each subgroup), and no difference was found in trends between complementary subgroups (male versus female, P = .53; adult versus child, P = .66). No statistically significant changes were found in use of ultrasound or MRI over the study period. With increasing BMI, CT was more frequently used.Of those diagnosed with appendicitis at an academic medical center, CT use increased more than 20-fold. However, no statistically significant trend was found for increased use of ultrasound or MRI.

Purpose We aimed to determine the agreement between quantitative susceptibility mapping (QSM)-based biomagnetic liver susceptometry (BLS) and confounder-corrected R2* mapping with superconducting quantum interference device (SQUID)-based biomagnetic liver susceptometry in patients with liver iron overload. Methods Data were acquired from two healthy controls and 22 patients undergoing MRI and SQUID-BLS as part of routine monitoring for iron overload. Magnetic resonance imaging was performed on a 3T system using a three-dimensional multi-echo gradient-echo acquisition. Both magnetic susceptibility and R2* of the liver were estimated from this acquisition. Linear regression was used to compare estimates of QSM-BLS and R2* to SQUID-BLS. Results Both QSM-BLS and confounder-corrected R2* were sensitive to the presence of iron in the liver. Linear regression between QSM-BLS and SQUID-BLS demonstrated the following relationship: QSM-BLS = (−0.22 ± 0.11) + (0.49 ± 0.05) · SQUID-BLS with r2 = 0.88. The coefficient of determination between liver R2* and SQUID-BLS was also r2 = 0.88. Conclusion We determined a strong correlation between both QSM-BLS and confounder-corrected R2* to SQUID-BLS. This study demonstrates the feasibility of QSM-BLS and confounder-corrected R2* for assessing liver iron overload, particularly when SQUID systems are not accessible. Magn Reson Med 78:264–270, 2017. © 2016 International Society for Magnetic Resonance in Medicine

Purpose To evaluate the accuracy of R2* models (1/T2* = R2*) for chemical shift-encoded magnetic resonance imaging (CSE-MRI)-based proton density fat-fraction (PDFF) quantification in patients with fatty liver and iron overload, using MR spectroscopy (MRS) as the reference standard. Materials and Methods Two Monte Carlo simulations were implemented to compare the root-mean-squared-error (RMSE) performance of single-R2* and dual-R2* correction in a theoretical liver environment with high iron. Fatty liver was defined as hepatic PDFF >5.6% based on MRS; only subjects with fatty liver were considered for analyses involving fat. From a group of 40 patients with known/suspected iron overload, nine patients were identified at 1.5T, and 13 at 3.0T with fatty liver. MRS linewidth measurements were used to estimate R2* values for water and fat peaks. PDFF was measured from CSE-MRI data using single-R2* and dual-R2* correction with magnitude and complex fitting. Results Spectroscopy-based R2* analysis demonstrated that the R2* of water and fat remain close in value, both increasing as iron overload increases: linear regression between R2*W and R2*F resulted in slope = 0.95 [0.79–1.12] (95% limits of agreement) at 1.5T and slope = 0.76 [0.49–1.03] at 3.0T. MRI-PDFF using dual-R2* correction had severe artifacts. MRI-PDFF using single-R2* correction had good agreement with MRS-PDFF: Bland–Altman analysis resulted in –0.7% (bias) ± 2.9% (95% limits of agreement) for magnitude-fit and –1.3% ± 4.3% for complex-fit at 1.5T, and –1.5% ± 8.4% for magnitude-fit and –2.2% ± 9.6% for complex-fit at 3.0T. Conclusion Single-R2* modeling enables accurate PDFF quantification, even in patients with iron overload. Level of Evidence: 1 J. Magn. Reson. Imaging 2017;45:428–439.

PURPOSE To develop an externally calibrated parallel imaging technique for three-dimensional multispectral imaging (3D-MSI) in the presence of metallic implants. THEORY AND METHODS A fast, ultrashort echo time (UTE) calibration acquisition is proposed to enable externally calibrated parallel imaging techniques near metallic implants. The proposed calibration acquisition uses a broadband radiofrequency (RF) pulse to excite the off-resonance induced by the metallic implant, fully phase-encoded imaging to prevent in-plane distortions, and UTE to capture rapidly decaying signal. The performance of the externally calibrated parallel imaging reconstructions was assessed using phantoms and in vivo examples. RESULTS Phantom and in vivo comparisons to self-calibrated parallel imaging acquisitions show that significant reductions in acquisition times can be achieved using externally calibrated parallel imaging with comparable image quality. Acquisition time reductions are particularly large for fully phase-encoded methods such as spectrally resolved fully phase-encoded three-dimensional (3D) fast spin-echo (SR-FPE), in which scan time reductions of up to 8 min were obtained. CONCLUSION A fully phase-encoded acquisition with broadband excitation and UTE enabled externally calibrated parallel imaging for 3D-MSI, eliminating the need for repeated calibration regions at each frequency offset. Significant reductions in acquisition time can be achieved, particularly for fully phase-encoded methods like SR-FPE. Magn Reson Med 77:2303-2309, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Purpose To evaluate the incidence and severity of potentially thrombus mimicking, flow-induced misallocation artifacts in a clinical setting. Two-point “Dixon” fat–water separation methods, with bipolar readout gradients, may suffer from flow-induced fat–water misallocation artifacts. If these artifacts occur within blood vessels, they may mimic thrombus. Materials and Methods Two-point Dixon coronal and axial images acquired in 102 consecutive patients were retrospectively evaluated for the presence of flow-induced artifacts in arteries and veins. Artifacts were graded on a 3-point scale (none, mild, severe) by two independent readers. Interreader agreement was evaluated with kappa statistics. Results Reader 1 reported 63 artifacts in 46 (45%) of the cases (severe in 19 cases, 18.6%). Reader 2 reported 51 artifacts in 43 (42.2%) of the cases (severe in 18 cases, 17.6%). Misallocation of fat and water was apparent in all datasets with severe artifacts, whereas variable signal intensity changes in water and fat images were observed in mild artifacts. Interreader agreement was good for artifacts appearing in coronal images (κ = 0.7) and fair for artifact appearance in axial images (κ = 0.24). Conclusion Our study shows a high incidence of flow-induced mild and severe artifacts in a two-point Dixon method with bipolar readout gradients. This artifact should not be misinterpreted as intravascular thrombus. Level of Evidence: 3 J. Magn. Reson. Imaging 2017;45:229–236.

Purpose To investigate the feasibility of estimating the proton-density fat fraction (PDFF) using a 7.1T magnetic resonance imaging (MRI) system and to compare the accuracy of liver fat quantification using different fitting approaches. Materials and methods Fourteen leptin-deficient ob/ob mice and eight intact controls were examined in a 7.1T animal scanner using a 3D six-echo chemical shift-encoded pulse sequence. Confounder-corrected PDFF was calculated using magnitude (magnitude data alone) and combined fitting (complex and magnitude data). Differences between fitting techniques were compared using Bland-Altman analysis. In addition, PDFFs derived with both reconstructions were correlated with histopathological fat content and triglyceride mass fraction using linear regression analysis. Results The PDFFs determined with the use of both reconstructions correlated very strongly (r = 0.91). However, small mean bias between reconstructions demonstrated divergent results (3.9%; confidence interval [CI] 2.7-5.1%). For both reconstructions, there was linear correlation with histopathology (combined fitting: r = 0.61; magnitude fitting: r = 0.64) and triglyceride content (combined fitting: r = 0.79; magnitude fitting: r = 0.70). Conclusion Liver fat quantification using the PDFF derived from MRI performed at 7.1T is feasible. PDFF has strong correlations with histopathologically determined fat and with triglyceride content. However, small differences between PDFF reconstruction techniques may impair the robustness and reliability of the biomarker at 7.1T. J. Magn. Reson. Imaging 2016;44:1425-1431.

Author(s): Hernando, Diego; Sharma, Samir D; Aliyari Ghasabeh, Mounes; Alvis, Bret D; Arora, Sandeep S; Hamilton, Gavin; Pan, Li; Shaffer, Jean M; Sofue, Keitaro; Szeverenyi, Nikolaus M; Welch, E Brian; Yuan, Qing; Bashir, Mustafa R; Kamel, Ihab R; Rice, Mark J; Sirlin, Claude B; Yokoo, Takeshi; Reeder, Scott B | Abstract: PurposeTo evaluate the accuracy and reproducibility of quantitative chemical shift-encoded (CSE) MRI to quantify proton-density fat-fraction (PDFF) in a fat-water phantom across sites, vendors, field strengths, and protocols.MethodsSix sites (Philips, Siemens, and GE Healthcare) participated in this study. A phantom containing multiple vials with various oil/water suspensions (PDFF:0%-100%) was built, shipped to each site, and scanned at 1.5T and 3T using two CSE protocols per field strength. Confounder-corrected PDFF maps were reconstructed using a common algorithm. To assess accuracy, PDFF bias and linear regression with the known PDFF were calculated. To assess reproducibility, measurements were compared across sites, vendors, field strengths, and protocols using analysis of covariance (ANCOVA), Bland-Altman analysis, and the intraclass correlation coefficient (ICC).ResultsPDFF measurements revealed an overall absolute bias (across sites, field strengths, and protocols) of 0.22% (95% confidence interval, 0.07%-0.38%) and R2 g 0.995 relative to the known PDFF at each site, field strength, and protocol, with a slope between 0.96 and 1.02 and an intercept between -0.56% and 1.13%. ANCOVA did not reveal effects of field strength (P = 0.36) or protocol (P = 0.19). There was a significant effect of vendor (F = 25.13, P = 1.07 × 10-10 ) with a bias of -0.37% (Philips) and -1.22% (Siemens) relative to GE Healthcare. The overall ICC was 0.999.ConclusionCSE-based fat quantification is accurate and reproducible across sites, vendors, field strengths, and protocols. Magn Reson Med 77:1516-1524, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Purpose To develop a multiband radiofrequency (RF) excitation strategy for simultaneous excitation of multiple RF offsets to accelerate fully phase-encoded imaging near metallic prostheses. Methods Multiband RF excitation was designed and incorporated into a spectrally resolved fully phase-encoded (SR-FPE) imaging scheme. A triband (−6, 0, 6 kHz) acquisition was compared with three separate single-band acquisitions at the corresponding RF offsets with a phantom containing the head of a hip prosthesis. In vivo multiband data with continuous spectral coverage were acquired in the knee of a healthy volunteer with the head of a hip prosthesis placed posteriorly and in a volunteer with a total knee prosthetic implant. Results Phantom images acquired with triband excitation were essentially identical to the composite of three single-band excitations, but with an acceleration factor of three. In vivo multiband images of the healthy knee with adjacent metal demonstrated very good depiction of knee anatomy. In vivo images of the total knee replacement were successfully acquired, allowing visualization of native tissue with far less signal dropout than 2D-FSE. Conclusions FPE imaging with multiband excitation is feasible in the presence of extreme off-resonance. This approach can reduce scan time and/or increase off-resonance coverage, enabling in vivo FPE imaging near metallic prostheses over a broad off-resonance spectrum. Magn Reson Med 77:1223–1230, 2017. © 2016 International Society for Magnetic Resonance in Medicine

Ferumoxytol is an ultrasmall superparamagnetic iron oxide agent marketed for the treatment of anemia. There has been increasing interest in its properties as an MRI contrast agent as well as greater awareness of its adverse event profile. This mini-review summarizes the current state of knowledge of the risks of ferumoxytol and methods of administration.

To demonstrate the feasibility of free-breathing three-dimensional (3D) radial ultrashort echo time (UTE) magnetic resonance (MR) imaging in the simultaneous detection of pulmonary embolism (PE) and high-quality evaluation of lung parenchyma.The institutional animal care committee approved this study. A total of 12 beagles underwent MR imaging and computed tomography (CT) before and after induction of PE with autologous clots. Breath-hold 3D MR angiography and free-breathing 3D radial UTE (1.0-mm isotropic spatial resolution; echo time, 0.08 msec) were performed at 3 T. Two blinded radiologists independently marked and graded all PEs on a four-point scale (1 = low confidence, 4 = absolutely certain) on MR angiographic and UTE images. Image quality of pulmonary arteries and lung parenchyma was scored on a four-point-scale (1 = poor, 4 = excellent). Locations and ratings of emboli were compared with reference standard CT images by using an alternative free-response receiver operating characteristic curve (AFROC) method. Areas under the curve and image quality ratings were compared by using the F test and the Wilcoxon signed-rank test.A total of 48 emboli were detected with CT. Both readers showed higher sensitivity for PE detection with UTE (83% and 79%) than with MR angiography (75% and 71%). The AFROC area under the curve was higher for UTE than for MR angiography (0.95 vs 0.89), with a significant difference in area under the curve of 0.06 (95% confidence interval: 0.01, 0.11; P = .018). UTE image quality exceeded that of MR angiography for subsegmental arteries (3.5 ± 0.7 vs 2.9 ± 0.5, P = .002) and lung parenchyma (3.8 ± 0.5 vs 2.2 ± 0.2, P.001). The apparent signal-to-noise ratio in pulmonary arteries and lung parenchyma was significantly higher for UTE than for MR angiography (41.0 ± 5.2 vs 24.5 ± 6.2 [P.001] and 10.2 ± 1.8 vs 3.5 ± 0.8 [P.001], respectively). The apparent contrast-to-noise ratio between arteries and PEs was higher for UTE than for MR angiography (20.3 ± 5.2 vs 15.4 ± 6.7, P = .055).In a canine model, free-breathing 3D radial UTE performs better than breath-hold 3D MR angiography in the detection of PE and yields better image quality for visualization of small vessels and lung parenchyma. Free-breathing 3D radial UTE for detection of PE is feasible and warrants evaluation in human subjects.

Waldenstrom’s macroglobulinemia (WM) is a lymphoplasmacytic lymphoma characterized by monocloncal IgM gammopathy and bone marrow infiltration [1]. First-line treatment has traditionally consisted o...

Author(s): Covarrubias, Yesenia; Fowler, Kathryn J; Mamidipalli, Adrija; Hamilton, Gavin; Wolfson, Tanya; Leinhard, Olof Dahlqvist; Jacobsen, Garth; Horgan, Santiago; Schwimmer, Jeffrey B; Reeder, Scott B; Sirlin, Claude B | Abstract: BACKGROUND:Quantitative-chemical-shift-encoded (CSE)-MRI methods have been applied to the liver. The feasibility and potential utility CSE-MRI in monitoring changes in pancreatic proton density fat fraction (PDFF) have not yet been demonstrated. PURPOSE:To use quantitative CSE-MRI to estimate pancreatic fat changes during a weight-loss program in adults with severe obesity and nonalcoholic fatty liver disease (NAFLD). To explore the relationship of reduction in pancreatic PDFF with reductions in anthropometric indices. STUDY TYPE:Prospective/longitudinal. POPULATION:Nine adults with severe obesity and NAFLD enrolled in a weight-loss program. FIELD STRENGTH/SEQUENCE:CSE-MRI fat quantification techniques and multistation-volumetric fat/water separation techniques were performed at 3 T. ASSESSMENT:PDFF values were recorded from parametric maps colocalized across timepoints. STATISTICAL TESTS:Rates of change of log-transformed variables across time were determined (linear-regression), and their significance assessed compared with no change (Wilcoxon test). Rates of change were correlated pairwise (Spearman's correlation). RESULTS:Mean pancreatic PDFF decreased by 5.7% (range 0.7-17.7%) from 14.3 to 8.6%, hepatic PDFF by 11.4% (2.6-22.0%) from 14.8 to 3.4%, weight by 30.9 kg (17.3-64.2 kg) from 119.0 to 88.1 kg, body mass index by 11.0 kg/m2 (6.3-19.1 kg/m2 ) from 44.1 to 32.9 kg/m2 , waist circumference (WC) by 25.2 cm (4.0-41.0 cm) from 133.1 to 107.9 cm, HC by 23.5 cm (4.5-47.0 cm) from 135.8 to 112.3 cm, visceral adipose tissue (VAT) by 2.9 L (1.7-5.7 L) from 7.1 to 4.2 L, subcutaneous adipose tissue (SCAT) by 4.0 L (2.9-7.4 L) from 15.0 to 11.0 L. Log-transformed rate of change for pancreatic PDFF was moderately correlated with log-transformed rates for hepatic PDFF, VAT, SCAT, and WC (ρ = 0.5, 0.47, 0.45, and 0.48, respectively), although not statistically significant. DATA CONCLUSION:Changes in pancreatic PDFF can be estimated by quantitative CSE-MRI in adults undergoing a weight-loss surgery program. Pancreatic and hepatic PDFF and anthropometric indices decreased significantly. LEVEL OF EVIDENCE:2 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2019;50:1092-1102.

Background Waldenstrom macroglobulinemia (WM) is a rare and incurable lymphoproliferative disease. The advent of novel therapies such as proteasome inhibitors and monoclonal antibodies has expanded the therapeutic armamentarium for treatment of WM. Due to the rare nature of the disease, most reported studies on the use of autologous stem cell transplant (ASCT) in WM are small and retrospective in nature. Since the advent of novel agents, few studies have reported whether these agents influence the disease course in the ASCT setting. Herein we present outcomes of patients with WM who underwent ASCT at three Mayo Clinic sites. Methods Records of all patients with WM who underwent ASCT between 8/2005 and 11/2017 were reviewed. Time-to-event analyses were performed from ASCT using the Kaplan-Meier method. Response criteria from the 6th International WM Workshop were used. Results Patient characteristics are described in Table 1. Two patients had large cell transformation; one prior to ASCT and one post-ASCT. The overall response rate to transplant was 100% (3 complete responses [CR], 8 very good partial responses [VGPR] and 6 partial responses [PR]). After a median follow-up of 58 months, the median progression free survival (PFS) after ASCT was 66 months and the median overall survival (OS) was not reached (NR). The relapse rate was 65% (11 out of 17 patients relapsed). The treatment related mortality was 0% and relapse mortality was 12%. The 2 deaths in the cohort were the patients who had large cell transformation and they died at 18 and 25 m post-ASCT, respectively. The treatment immediately prior to transplant, irrespective of the use of rituximab (R), did not impact the PFS (median PFS 47 m with prior R v 66 m without prior R, p=0.82, Fig. 1A). Similarly, prior exposure to a bortezomib (V)-based regimen did not impact the PFS (median NR v. 47 m, p=0.19 respectively, Fig. 1B). Achieving ≥VGPR after ASCT did not result in superior PFS compared to patients who achieved a PR (47 m vs. NR, p=0.59, respectively, Fig. 1C). Patients who had ASCT after >2 lines of therapy had an inferior PFS compared to patients who had ASCT ≤2 lines of therapy (41 m vs. 112 m, p=0.03, respectively, Fig 1D). Patients with large cell transformation at any point, had inferior PFS after transplant compared to those who did not (10m vs. 66m, p Conclusions ASCT for patients with WM is a safe and efficacious treatment modality with an ORR of 100% and affords eligible patients a median treatment-free interval of 4 years. The use of V or R prior to ASCT does not impact the depth of response or PFS after ASCT. To obtain the maximum PFS benefit, ASCT should be performed earlier in the disease course, prior to receiving more than 2 lines of therapy.

PURPOSE: To investigate the correspondence between arterial spin labeling (ASL) flow-sensitive alternating inversion recovery (FAIR) and ferumoxytol dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI) for the assessment of placental intervillous perfusion. METHODS: Ten pregnant macaques in late 2(nd) trimester were imaged at 3T using a 2D ASL FAIR, with and without outer volume saturation (OVS) pulses used to control the bolus width, and a 3D ferumoxytol DCE MRI acquisition. ASL tagged/control pairs were averaged, subtracted, and normalized to create perfusion ratio maps. Contrast arrival time and uptake slope were estimated by fitting DCE data to a sigmoid function. Macaques (N=4) received interleukin-1β to induce inflammation and disrupt perfusion. RESULTS: FAIR tag modification with OVS reduced median ASL ratio percentage compared to conventional FAIR (0.64±1.42% vs. 0.71±2.00%;p0.05). CONCLUSION: ASL FAIR and ferumoxytol DCE MRI are feasible methods to detect early blood delivery to the macaque placenta. OVS reduced high macrovascular ASL signal. Interleukin-1β exposure did not alter placental intervillous perfusion. An endogenous-labeling perfusion technique is limited due to extended transit times for flow within the placenta beyond the immediate vicinity of the maternal spiral arteries.

Ixazomib is the first oral proteasome inhibitor to enter the clinic. Given the efficacy of bortezomib in combination with cyclophosphamide and dexamethasone, we studied the combination of ixazomib, cyclophosphamide and dexamethasone (ICd) in newly diagnosed multiple myeloma (NDMM) and patients with measurable disease, irrespective of transplant eligibility, were enrolled. The phase 1 was to determine the maximum tolerated dose (MTD) of cyclophosphamide in the combination. Patients received ixazomib 4 mg (days 1, 8, 15), dexamethasone 40 mg (days 1, 8, 15, 22), and cyclophosphamide 300 or 400 mg/m2 days 1, 8, 15, 22; cycles were 28 days. We enrolled 51 patients, 10 in phase 1 and 41 patients in phase 2. The median age was 64.5 years (range: 41–88); 29% had high or intermediate risk FISH. The MTD was 400 mg/m2 of cyclophosphamide weekly. The best confirmed response in all 48 patients included ≥ partial response in 77%, including ≥ VGPR in 35%; 3 patients had a sCR. The response rate for all 48 evaluable patients at 4-cycles was 71%; the median time to response was 1.9 months. Common adverse events included cytopenias, fatigue and GI intolerance. ICd is a convenient, all oral combination that is well tolerated and effective in NDMM.

PURPOSE: To compare the accuracy of magnetic resonance (MR) imaging with that of computed tomography (CT) for the diagnosis of acute appendicitis in emergency department (ED) patients. MATERIALS AND METHODS: This was an institutional review board–approved, prospective, observational study of ED patients at an academic medical center (February 2012 to August 2014). Eligible patients were nonpregnant and 12- year-old or older patients in whom a CT study had been ordered for evaluation for appendicitis. After informed consent was obtained, CT and MR imaging (with non–contrast material–enhanced, diffusion-weighted, and intravenous contrast-enhanced sequences) were performed in tandem, and the images were subsequently retrospectively interpreted in random order by three abdominal radiologists who were blinded to the patients’ clinical outcomes. Likelihood of appendicitis was rated on a five-point scale for both CT and MR imaging. A composite reference standard of surgical and histopathologic results and clinical follow-up was used, arbitrated by an expert panel of three investigators. Test characteristics were calculated and reported as point estimates with 95% confidence intervals (CIs). RESULTS: Analysis included images of 198 patients (114 women [58%]; mean age, 31.6 years ± 14.2 [range, 12–81 years]; prevalence of appendicitis, 32.3%). The sensitivity and specificity were 96.9% (95% CI: 88.2%, 99.5%) and 81.3% (95% CI: 73.5%, 87.3%) for MR imaging and 98.4% (95% CI: 90.5%, 99.9%) and 89.6% (95% CI: 82.8%, 94.0%) for CT, respectively, when a cutoff point of 3 or higher was used. The positive and negative likelihood ratios were 5.2 (95% CI: 3.7, 7.7) and 0.04 (95% CI: 0, 0.11) for MR imaging and 9.4 (95% CI: 5.9, 16.4) and 0.02 (95% CI: 0.00, 0.06) for CT, respectively. Receiver operating characteristic curve analysis demonstrated that the optimal cutoff point to maximize accuracy was 4 or higher, at which point there was no difference between MR imaging and CT. CONCLUSION: The diagnostic accuracy of MR imaging was similar to that of CT for the diagnosis of acute appendicitis. © RSNA, 2018

Over the last two decades, the utilization of various novel therapies in the upfront or salvage settings has continued to improve survival outcomes for patients with Multiple Myeloma (MM). Thus, the conventional role for hematopoietic stem cell transplantation (HSCT) in MM either in the form of an autologous stem cell transplant (ASCT) or an allogeneic stem cell transplant (Allo-SCT) warrants re-evaluation, given the aforementioned clinical advances. Here, we present a consensus statement of our multidisciplinary group of over 30 Mayo Clinic physicians with a special interest in the care of patients with MM and provide evidence-based recommendations on the use of HSCT in MM. We specifically address topics that include the role and timing of an ASCT for MM in the era of novel agents, eligibility for an ASCT, post-ASCT consolidation, and maintenance options, and finally the utility of an upfront tandem ASCT, salvage second ASCT, and an allo-SCT in MM.

Background Treatment outcomes have improved in lymphoid malignancies but relapse remains inevitable for most patients. Everolimus and lenalidomide have shown clinical activity as single agents in patients with relapsed and refractory Hodgkin and non-Hodgkin lymphomas. Patients and Methods The present phase I/II trial for patients with relapsed and refractory lymphoid malignancy opened at Mayo Clinic from January 2011 to May 2013. The trial used a standard cohort 3 + 3 design to determine the maximum tolerated dose for the combination. Stem cell transplantation had failed in 27 of the patients (49%), 63% had stage IV disease, and ≥ 3 previous therapies had failed in 78%. Results Of the 58 patients, enrolled, 55 were evaluable for analysis. The maximum tolerated dose was 5 mg/d for everolimus plus 10 mg/d for 21 days for lenalidomide. The most common grade ≥ 3 toxicities were hematologic and included neutropenia (56%), leukopenia (38%), and thrombocytopenia (33%). Seven patients discontinued the study because of adverse events. One patient died of disease progression. The overall response rate was 27% (15 of 55), with 38% (21 of 55) having stable disease. Conclusion The present phase I/II trial of everolimus and lenalidomide for R/R lymphoma has shown the combination to be tolerable, with neutropenia as the main dose-limiting toxicity. Encouraging responses were seen in this heavily pretreated group, and the patients with a response had meaningful duration of response.

BackgroundClinical trials utilizing proton density fat fraction (PDFF) as an imaging biomarker for hepatic steatosis have used a laborious region-of-interest (ROI) sampling strategy of placing an ROI in each hepatic segment.PurposeTo identify a strategy with the fewest ROIs that consistently achieves close agreement with the nine-ROI strategy.Study typeRetrospective secondary analysis of prospectively acquired clinical research data.PopulationA total of 391 adults (173 men, 218 women) with known or suspected NAFLD.Field strength/sequenceConfounder-corrected chemical-shift-encoded 3T MRI using a 2D multiecho gradient-recalled echo technique.AssessmentAn ROI was placed in each hepatic segment. Mean nine-ROI PDFF and segmental PDFF standard deviation were computed. Segmental and lobar PDFF were compared. PDFF was estimated using every combinatorial subset of ROIs and compared to the nine-ROI average.Statistical testingMean nine-ROI PDFF and segmental PDFF standard deviation were summarized descriptively. Segmental PDFF was compared using a one-way analysis of variance, and lobar PDFF was compared using a paired t-test and a Bland-Altman analysis. The PDFF estimated by every subset of ROIs was informally compared to the nine-ROI average using median intraclass correlation coefficients (ICCs) and Bland-Altman analyses.ResultsThe study population's mean whole-liver PDFF was 10.1 ± 8.9% (range: 1.1-44.1%). Although there was no significant difference in average segmental (P = 0.452) or lobar (P = 0.154) PDFF, left and right lobe PDFF differed by at least 1.5 percentage points in 25.1% (98/391) of patients. Any strategy with ≥4 ROIs had ICC >0.995. 115 of 126 four-ROI strategies (91%) had limits of agreement (LOA) 0.995, and 2/36 (6%) of two-ROI strategies and 46/84 (55%) of three-ROI strategies had LOA

Clinical Question Is rituximab maintenance therapy after first-line induction chemoimmunotherapy for follicular lymphoma associated with improved outcomes? Bottom Line Compared with observation, rituximab maintenance therapy prolongs progression-free survival without an improvement in overall survival or quality of life after first-line induction chemoimmunotherapy.

The hematologic response is critical in patients with light chain amyloidosis because a good response is known to improve organ response and overall survival. We present a retrospective analysis to compare the hematologic and organ response in patients who received bortezomib-based therapy before autologous stem cell transplantation (ASCT) versus those who received non-bortezomib-based therapy before ASCT and those who underwent ASCT at diagnosis.Of a total of 63 patients who underwent ASCT for light chain amyloidosis, 34 received bortezomib-based therapy before ASCT (Bor-ASCT) and 29 did not receive bortezomib therapy (non-Bor-ASCT). A greater number of patients had involvement of ≥ 3 organs and cardiac involvement in the Bor-ASCT group, suggesting a greater risk at baseline in the Bor-ASCT group.At 3, 6, and 12 months after ASCT, the hematologic response was better in the Bor-ASCT group, with a statistically significance difference at 6 months (partial response or better in 82% vs. 20%; P = .002) and 12 months (partial response or better in 76% vs. 33%; P = .02). Organ responses (66% vs. 21%; P .001) and median overall survival (not reached vs. 53 months; P = .001) were also greater in the Bor-ASCT group.Our study has shown that bortezomib-based therapy before ASCT improves the hematologic response, organ response and overall survival, potentially by decreasing the light chain load before ASCT.

The combination of pomalidomide (POM) and dexamethasone (DEX) was evaluated for relapsed/refractory primary central nervous system lymphoma (PCNSL) and primary vitreoretinal lymphoma (PVRL) to determine the maximal tolerated dose (MTD) of POM as the primary objective, and overall response rate (ORR), progression-free survival (PFS), and safety profile as secondary objectives. A cohorts-of-3 study design was used with a dose-escalation schedule consisting of POM (3, 5, 7, or 10 mg) orally daily for 21 days every 28 days and DEX 40 mg orally every week. After 2 cycles, POM was continued alone until disease progression, intolerance, or subject withdrawal. Following MTD determination, the MTD cohort was expanded. Twenty-five of 29 patients with the median of 3 prior treatments were eligible for assessment as per international PCNSL collaborative group criteria. The MTD of POM was 5 mg daily for 21 days every 28 days. Whole-study ORR was 48% (12 of 25; 95% confidence interval [CI], 27.8%, 68.7%) with 6 complete response (CR), 2 complete response, unconfirmed (CRu), and 4 partial response (PR). MTD cohort ORR was 50% (8 of 16; 95% CI, 24.7%, 75.4%) with 5 CR, 1 CRu, and 2 PR. Median PFS was 5.3 months (whole study) and 9 months (for responders). One patient had pseudoprogression. Grade 3/4 hematologic toxicities included neutropenia (21%), anemia (8%), and thrombocytopenia (8%). Grade 3/4 nonhematologic toxicities included lung infection (12%), sepsis (4%), fatigue (8%), syncope (4%), dyspnea (4%), hypoxia (4%), respiratory failure (8%), and rash (4%). POM/DEX treatment is feasible with significant therapeutic activity against relapsed/refractory PCNSL and PVRL. This trial was registered at www.clinicaltrials.gov as #NCT01722305.

Highlights • Hemophilic pseudotumor is a rare complication of Hemophilia A and B. • Diagnosis requires a high index of suspicion-especially in non-hemophilic patients. • Radiographic findings are similar to that of malignant tumors. • Surgical intervention remains the mainstay of treatment. • Pre-operative embolization has been shown to reduce intra-operative bleeding., Introduction Hemophilic pseudotumor is a rare but well documented complication seen in approximately 1–2% of patients with hemophilia. The incidence continues to decrease, likely because of increasingly sophisticated techniques in managing factor deficiency. We present a case of hemophilic pseudotumor in a patient without hemophilia, an exceptionally rare entity, and outline a hybrid approach to treatment. Presentation of case The patient presented with a left sided iliopsoas mass and associated radiculopathy, with a history of a poorly characterized bleeding diathesis and Noonan’s syndrome. He had no history of trauma and was not being treated with anti-coagulation. Of note, factors VIII, IX and XI were normal. An open biopsy was consistent with hemophilic pseudotumor. The patient underwent a hybrid procedure of preoperative embolization of the left internal iliac and left deep circumflex arteries followed by surgical debridement and resection, with an excellent outcome. Discussion Hemophilic pseudotumor is rarely seen in patients with hemophilia, and even less frequently in patients without. Trauma is often the inciting event. A high index of clinical suspicion is required in order to secure the diagnosis, as the radiographic appearance is non-specific. Our patient had no history of trauma, although we question whether his underlying bleeding diathesis may have predisposed him to developing the pseudotumor. Surgery remains the cornerstone of management in these cases. Conclusion Within the literature, there are only two other cases of hemophilic pseudotumor occurring in a non-hemophiliac patient, highlighting the rarity of this case and the associated diagnostic dilemma.

Purpose To perform a systematic review and meta-analysis of all published studies since 2005 that evaluate the accuracy of magnetic resonance imaging (MRI) for the diagnosis of acute appendicitis in the general population presenting to emergency departments. Materials and Methods All retrospective and prospective studies evaluating the accuracy of MRI to diagnose appendicitis published in English and listed in PubMed, Web of Science, Cinahl Plus, and the Cochrane Library since 2005 were included. Excluded studies were those without an explicitly stated reference standard, with insufficient data to calculate the study outcomes, or if the population enrolled was limited to pregnant women or children. Data were abstracted by one investigator and confirmed by another. Data included the number of true positives, true negatives, false positives, false negatives, number of equivocal cases, type of MRI scanner, type of MRI sequence, and demographic data including study setting and gender distribution. Summary test characteristics were calculated. Forest plots and a summary receiver operator characteristic plot were generated. Results Ten studies met eligibility criteria, representing patients from seven countries. Nine were prospective and two were multicenter studies. A total of 838 subjects were enrolled; 406 (48%) were women. All studies routinely used unenhanced MR images, although two used intravenous contrast-enhancement and three used diffusion-weighted imaging. Using a bivariate random-effects model the summary sensitivity was 96.6% (95% confidence interval [CI]: 92.3%–98.5%) and summary specificity was 95.9% (95% CI: 89.4%–98.4%). Conclusion MRI has a high sensitivity and specificity for the diagnosis of appendicitis, similar to that reported previously for computed tomography. J. Magn. Reson. Imaging 2016;43:1346–1354.

The objective of this study was to evaluate changes in liver fat content over time in asymptomatic adults and to investigate the factors that may influence these changes.Liver attenuation on unenhanced CT images of 1022 asymptomatic adults (556 women and 466 men; mean age at the time of the index CT examination, 56.7 years) was retrospectively measured on initial and surveillance CT colonography screening examinations (mean [± SD] interval, 5.5 ± 0.8 years). Changes in liver attenuation (expressed as Hounsfield units) were assessed according to various factors, including body mass index (BMI), age, and sex.Mean liver attenuation was 60.3 HU on the index CT scan and 58.4 HU on the 5-year follow-up CT scan (p0.0001). Changes in liver attenuation greater than 10 HU, 5-10 HU, and less than 5 HU were observed in 187 (18%), 212 (21%), and 623 (61%) individuals, respectively. Changes in attenuation greater than 10 HU were negative (i.e., fattier liver) in 130 of 187 individuals (70%) and were more likely to be associated with an increase in BMI (83 of 130 individuals [64%] vs 19 of 57 individuals [33%]; p0.0001). For changes in attenuation of 5 HU or more, negative (steatotic) changes outnumbered positive changes, occurring in 258 of 1022 individuals (25%) versus 141 of 1022 individuals (14%) (p0.0001). Changes in BMI were negatively correlated with changes in attenuation (p = 0.015). There was no statistically significant correlation between changes in attenuation and either age or sex. An improved lipid profile and the use of a lipid-lowering medication regimen correlated with an interval decrease in liver attenuation.Changes in liver attenuation over time, reflecting temporal changes in fat content, were quite variable in this asymptomatic adult population and were only partially explained by the factors examined. These observations may provide early insight into the natural history of incidental hepatic steatosis in asymptomatic adults.