Traceable dosimetry for MeV ion beams.

Standard dosimetry protocols exist for highly penetrating photon and particle beams used in the clinic and in research. However, these protocols cannot be directly applied to shallow penetration MeV-range ion beams. The Radiological Research Accelerator Facility has been using such beams for almost 50 years to irradiate cell monolayers, using self-developed dosimetry, based on tissue equivalent ionization chambers. To better align with the internationally accepted standards, we describe implementation of a commercial, NIST-traceable, air-filled ionization chamber for measurement of absorbed dose to water from low energy ions, using radiation quality correction factors calculated using TRS-398 recommendations. The reported dose does not depend on the ionization density in the range of 10-150 keV/µm.

Low Prevalence of Screen-Detected Colorectal Cancer in an Average-Risk Population: The New Normal.

Prior studies have reported the prevalence of colorectal cancer (CRC) in average-risk screening population ages 50-75 to be 0.7%-1.0%.1,2 However, no estimates from studies enrolling individuals undergoing screening colonoscopy have been reported. The experience of ongoing studies enrolling average-risk individuals is that the prevalence rates are substantially lower. A 2020 study from a community-based cohort undergoing CRC screening with fecal immunochemical testing followed by diagnostic colonoscopy reported a CRC prevalence rate of 1.46 per 1000, or 0.15%.3 The aim of our study is to report the screen-detected prevalence of CRC and advanced neoplasia in average-risk asymptomatic individuals from selected academic and community medical centers in the United States, Canada, and Germany and describe associated risk factors.

Necrosome-positive granulovacuolar degeneration is associated with TDP-43 pathological lesions in the hippocampus of ALS/FTLD cases.

AIM: Granulovacuolar degeneration (GVD) in Alzheimer's disease (AD) involves the necrosome, which is a protein complex consisting of phosphorylated receptor-interacting protein kinase 1 (pRIPK1), pRIPK3 and phosphorylated mixed lineage kinase domain-like protein (pMLKL). Necrosome-positive GVD was associated with neuron loss in AD. GVD was recently linked to the C9ORF72 mutation in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with transactive response DNA-binding protein (TDP-43) pathology (FTLD-TDP). Therefore, we investigated whether GVD in cases of the ALS-FTLD-TDP spectrum (ALS/FTLD) shows a similar involvement of the necrosome as in AD, and whether it correlates with diagnosis, presence of protein aggregates and cell death in ALS/FTLD. METHODS: We analysed the presence and distribution of the necrosome in post-mortem brain and spinal cord of ALS and FTLD-TDP patients (n = 30) with and without the C9ORF72 mutation, and controls (n = 22). We investigated the association of the necrosome with diagnosis, the presence of pathological protein aggregates and neuronal loss. RESULTS: Necrosome-positive GVD was primarily observed in hippocampal regions of ALS/FTLD cases and was associated with hippocampal TDP-43 inclusions as the main predictor of the pMLKL-GVD stage, as well as with the Braak stage of neurofibrillary tangle pathology. The central cortex and spinal cord, showing motor neuron loss in ALS, were devoid of any accumulation of pRIPK1, pRIPK3 or pMLKL. CONCLUSIONS: Our findings suggest a role for hippocampal TDP-43 pathology as a contributor to necrosome-positive GVD in ALS/FTLD. The absence of necroptosis-related proteins in motor neurons in ALS argues against a role for necroptosis in ALS-related motor neuron death.

Proton Irradiation Platforms for Preclinical Studies of High-Dose-Rate (FLASH) Effects at RARAF.

Limited availability of proton irradiators optimized for high-dose-rate studies makes the preclinical research of proton FLASH therapy challenging. We assembled two proton irradiation platforms that are capable of delivering therapeutic doses to thin biological samples at dose rates equal to and above 100 Gy/s. We optimized and tested dosimetry protocols to assure accurate dose delivery regardless of the instantaneous dose rate. The simplicity of the experimental setups and availability of custom-designed sample holders allows these irradiation platforms to be easily adjusted to accommodate different types of samples, including cell monolayers, 3D tissue models and small animals. We have also fabricated a microfluidic flow-through device for irradiations of biological samples in suspension. We present one example of a measurement with accompanying preliminary results for each of the irradiation platforms. One irradiator was used to study the role of proton dose rate on cell survival for three cancer cell lines, while the other was used to investigate the depletion of oxygen from an aqueous solution by water radiolysis using short intense proton pulses. No dose-rate-dependent variation was observed between the survival fractions of cancer cells irradiated at dose rates of 0.1, 10 and 100 Gy/s up to 10 Gy. On the other hand, irradiations of Fricke solution at 1,000 Gy/s indicated full depletion of oxygen after proton doses of 107 Gy and 56 Gy for samples equilibrated with 21% and 4% oxygen, respectively.

[Gene-specific treatment approaches in amyotrophic lateral sclerosis in the present and future]. / Genspezifische Therapieansätze bei amyotropher Lateralsklerose in Gegenwart und Zukunft.

Amyotrophic lateral sclerosis (ALS) is monogenic in up to 10% of cases. Various mutation types result in a loss of function, a gain of toxicity or a combination of both. Due to the continuous development of gene-specific approaches, the treatment of the various ALS forms is no longer a dream. Depending on the underlying mutation type and pathomechanism, different antisense oligonucleotide (ASO)-based or viral strategies are available. The SOD1 and C9ORF72 genes are the most frequently mutated ALS genes in Germany and their mutations most likely predominantly lead to a gain of toxicity. For both genes, specific ASOs were developed binding to the respective mRNAs and leading to their degradation and are now being tested in clinical trials after excellent efficacy in the related ALS mouse models, with promising interim results. For the sporadic form of ALS there are also gene-specific approaches that compensate pathomechanisms and are a promising therapeutic option. In this article, gene-specific therapeutic developments in ALS as well as possible pitfalls and challenges are discussed in detail.

Tuning friction and slip at solid-nanoparticle suspension interfaces by electric fields.

We report an experimental Quartz Crystal Microbalance (QCM) study of tuning interfacial friction and slip lengths for aqueous suspensions of TiO2 and Al2O3 nanoparticles on planar platinum surfaces by external electric fields. Data were analyzed within theoretical frameworks that incorporate slippage at the QCM surface electrode or alternatively at the surface of adsorbed particles, yielding values for the slip lengths between 0 and 30 nm. Measurements were performed for negatively charged TiO2 and positively charged Al2O3 nanoparticles in both the absence and presence of external electric fields. Without the field the slip lengths inferred for the TiO2 suspensions were higher than those for the Al2O3 suspensions, a result that was consistent with contact angle measurements also performed on the samples. Attraction and retraction of particles perpendicular to the surface by means of an externally applied field resulted in increased and decreased interfacial friction levels and slip lengths. The variation was observed to be non-monotonic, with a profile attributed to the physical properties of interstitial water layers present between the nanoparticles and the platinum substrate.

The Dietary Inflammatory Index® and Alternative Healthy Eating Index 2010 in relation to leucocyte telomere length in postmenopausal women: a cross-sectional study.

Telomeres are nucleoprotein complexes that form the ends of eukaryotic chromosomes where they protect DNA from genomic instability, prevent end-to-end fusion and limit cellular replicative capabilities. Increased telomere attrition rates, and relatively shorter telomere length, is associated with genomic instability and has been linked with several chronic diseases, malignancies and reduced longevity. Telomeric DNA is highly susceptible to oxidative damage and dietary habits may make an impact on telomere attrition rates through the mediation of oxidative stress and chronic inflammation. The aim of this study was to examine the association between leucocyte telomere length (LTL) with both the Dietary Inflammatory Index® 2014 (DII®) and the Alternative Healthy Eating Index 2010 (AHEI-2010). This is a cross-sectional analysis using baseline data from 263 postmenopausal women from the Alberta Physical Activity and Breast Cancer Prevention (ALPHA) Trial, in Calgary and Edmonton, Alberta, Canada. No statistically significant association was detected between LTL z-score and the AHEI-2010 (P = 0·20) or DII® (P = 0·91) in multivariable adjusted models. An exploratory analysis of AHEI-2010 and DII® parameters and LTL revealed anthocyanidin intake was associated with LTL (P < 0·01); however, this association was non-significant after a Bonferroni correction was applied (P = 0·27). No effect modification by age, smoking history, or recreational physical activity was detected for either relationship. Increased dietary antioxidant and decreased oxidant intake were not associated with LTL in this analysis.

LET dependent response of GafChromic films investigated with MeV ion beams.

The change in optical properties of GafChromic films depends not only on the absorbed dose, but also on the linear energy transfer (LET) of the ionizing radiation. The influence of LET on the film dose-response relationship is especially important when films are applied for dosimetry of energetic charged particles. In the present study, we examined the response of the unlaminated EBT3 and MD-V3 films to proton, deuterium and helium beams with energies in the range of several megaelectronvolts (MeV). Films were exposed to doses up to 200 Gy and a model based on the bimolecular chemical reaction was chosen to fit the measured film signals. The LET in the active layers of the films and the dose correction factors were computed with Monte Carlo software TRIM. Signal quenching, observed for all ion beams in comparison to x-rays, was investigated as a function of the LET in the range of 10-100 keV µm-1. The response of the films got weaker with increasing the LET and showed no dependence on the ion species. The LET effect was quantified by introducing a modified expression for the relative effectiveness (RE) by which a unique RE value is assigned to a single LET. The RE defined in that way decreased from about 90% for LET of 10 keV µm-1 to less than 50% for LET of 100 keV µm-1. Similar behavior was observed for EBT3 and MD-V3 film models.

Fascial layers influence the spread of injectate during ultrasound-guided infraclavicular brachial plexus block: a cadaver study.

BACKGROUND: Fascial layers of the neurovascular sheath containing the brachial plexus influence distribution of local anaesthetic, hence increasing the risk of block failure when performing infraclavicular brachial plexus block (ICB). METHODS: Ultrasound-guided infraclavicular brachial plexus block was performed on cadavers using a single injection technique with dye (20-30 ml). After injection, we carried out consecutive dissection of the neurovascular bundle to study dye injectate spread and identify the presence of fascial layers. Ultrasound video images (scout scan and injection) and recordings of dissections were evaluated by independent experts (regional anaesthetists and anatomists). RESULTS: Well defined fascial layers were identified at dissection in seven out of 12 infraclavicular spaces studied. These fascial layers impeded the spread of dye injectate substantially in six cases and partially in one case. No fascial layers were identified at dissection in five cases, in each of which the spread of injectate was complete throughout the neurovascular bundle. The sensitivity and specificity of ultrasonography and haptic sensation for detection of fascial layers were poor. CONCLUSIONS: When fascial layers are present in the neurovascular sheath, they impede the spread of injectate during infraclavicular brachial plexus block. Ultrasound detection of these fascial layers is unreliable in cadavers. These findings support the use of greater volumes of injectate or a multiple injection technique when performing this block.

Radar plots: A novel modality for displaying disparate data on the efficacy of eluxadoline for the treatment of irritable bowel syndrome with diarrhea.

BACKGROUND: Patients with irritable bowel syndrome with diarrhea (IBS-D) experience a range of abdominal and bowel symptoms; successful management requires alleviation of this constellation of symptoms. Eluxadoline, a locally active mixed µ- and κ-opioid receptor agonist and δ-opioid receptor antagonist, is approved for the treatment of IBS-D in adults based on the results of 2 Phase 3 studies. Radar plots can facilitate comprehensive, visual evaluation of diverse but interrelated efficacy endpoints. METHODS: Two double-blind, placebo-controlled, Phase 3 trials (IBS-3001 and IBS-3002) randomized patients meeting Rome III criteria for IBS-D to twice-daily eluxadoline 75 or 100 mg or placebo. Radar plots were prepared showing pooled Weeks 1-26 response rates for the primary efficacy composite endpoint (simultaneous improvement in abdominal pain and stool consistency), stool consistency, abdominal pain, urgency-free days, and adequate relief, and change from baseline to Week 26 in IBS-D global symptom score, abdominal discomfort, abdominal pain, abdominal bloating, and daily number of bowel movements. KEY RESULTS: The studies enrolled 2428 patients. Eluxadoline increased Weeks 1-26 responder proportions vs placebo for the composite endpoint, stool consistency, abdominal pain, urgency-free days, and adequate relief. Changes from baseline to Week 26 in IBS-D global symptom score, abdominal discomfort, abdominal pain, abdominal bloating, and number of bowel movements were greater with eluxadoline vs placebo. CONCLUSIONS AND INFERENCES: Data presentation in radar plot format facilitates interpretation across multiple domains, demonstrating that eluxadoline treatment led to improvements vs placebo across 13 endpoints representing the range of symptoms experienced by patients with IBS-D.

A Horizontal Multi-Purpose Microbeam System.

A horizontal multi-purpose microbeam system with a single electrostatic quadruplet focusing lens has been developed at the Columbia University Radiological Research Accelerator Facility (RARAF). It is coupled with the RARAF 5.5 MV Singleton accelerator (High Voltage Engineering Europa, the Netherlands) and provides micrometer-size beam for single cell irradiation experiments. It is also used as the primary beam for a neutron microbeam and microPIXE (particle induced x-ray emission) experiment because of its high particle fluence. The optimization of this microbeam has been investigated with ray tracing simulations and the beam spot size has been verified by different measurements.

Abnormal esophageal acid exposure on high-dose proton pump inhibitor therapy is common in systemic sclerosis patients.

BACKGROUND: Esophageal dysfunction and gastro-esophageal reflux disease (GERD) are common among patients with systemic sclerosis (SSc). Although high-dose proton pump inhibitors (PPIs) typically normalize esophageal acid exposure, the effectiveness of PPI therapy has not been systematically studied in SSc patients. The aim of this study was to characterize reflux in SSc patients on high-dose PPI using esophageal pH-impedance testing. METHODS: In this case-controlled retrospective analysis, 38 patients fulfilling 2013 American College of Rheumatology SSc criteria who underwent esophageal pH-impedance testing on twice-daily PPI between January 2014 and March 2017 at a tertiary referral center were compared with a control-cohort of 38 non-SSc patients matched for PPI formulation and dose, hiatal hernia size, age, and gender. Patient clinical characteristics, including endoscopy and high-resolution manometry findings, were assessed via chart review. KEY RESULTS: On pH-impedance, SSc patients had higher acid exposure times (AETs) than controls. Sixty-one percent of the SSc patients and 18% of the control patients had a total AET ≥4.5% (P < .001). Systemic sclerosis patients also had significantly longer AETs, longer median bolus clearance, and lower nocturnal impedance values. CONCLUSIONS & INFERENCES: Abnormal esophageal acid exposure despite high-dose PPI therapy was common among patients with SSc. The lack of increased reflux episodes in the SSc patients, and longer bolus clearance times and lower nocturnal impedance, supports ineffective clearance as the potential mechanism. Systemic sclerosis patients may require adjunctive therapies to PPIs to control acid reflux.

Dose-response effects of aerobic exercise on energy compensation in postmenopausal women: combined results from two randomized controlled trials.

BACKGROUND/OBJECTIVES: Despite the clear health benefits of exercise, exercised-induced weight loss is often less than expected. The term 'exercise energy compensation' is used to define the amount of weight loss below what is expected for the amount of exercise energy expenditure. We examined the dose-response effects of exercise volume on energy compensation in postmenopausal women. PARTICIPANTS/METHODS: Data from Alberta Physical Activity and Breast Cancer Prevention (ALPHA) and Breast Cancer and Exercise Trial in Alberta (BETA) were combined for the present analysis. The ALPHA and BETA trials were two-centred, two-armed, 12-month randomized controlled trials. The ALPHA trial included 160 participants randomized to 225 min per week of aerobic exercise, and the BETA trial randomized 200 participants to each 150 and 300 min per week of aerobic exercise. All participants were aged 50-74 years, moderately inactive (<90 min per week of exercise), had no previous cancer diagnosis and a body mass index between 22 and 40 kg m-2. Energy compensation was based on changes in body composition (dual-energy X-ray absorptiometry scan) and estimated exercise energy expenditure from completed exercise volume. Associations between Δenergy intake, ΔVO2peak and Δphysical activity time with energy compensation were assessed. RESULTS: No differences in energy compensation were noted between interventions. However, there were large inter-individual differences in energy compensation between participants; 9.4% experienced body composition changes that were greater than expected based on exercise energy expenditure, 64% experienced some degree of energy compensation and 26.6% experienced weight gain based on exercise energy expenditure. Increases in VO2peak were associated with reductions in energy compensation (ß=-3.44 ml kg-1 min-1, 95% confidence interval for ß=-4.71 to -2.17 ml kg-1 min-1; P=0.0001). CONCLUSIONS: Large inter-individual differences in energy compensation were noted, despite no differences between activity doses. In addition, increases in VO2peak were associated with lower energy compensation. Future studies are needed to identify behavioral and metabolic factors that may contribute to this large inter-individual variability in energy compensation.

Effects of Radiation Exposure on the Cost-Effectiveness of CT Angiography and Perfusion Imaging in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND AND PURPOSE: CT angiography and perfusion imaging is an important prognostic tool in the management of patients with aneurysmal subarachnoid hemorrhage. The purpose of this study was to perform a cost-effectiveness analysis of advanced imaging in patients with SAH, incorporating the risks of radiation exposure from CT angiography and CT perfusion imaging. MATERIALS AND METHODS: The risks of radiation-induced brain cancer and cataracts were incorporated into our established decision model comparing the cost-effectiveness of CT angiography and CT perfusion imaging and transcranial Doppler sonography in SAH. Cancer risk was calculated by using National Cancer Institute methodology. The remaining input probabilities were based on literature data and a cohort at our institution. Outcomes were expected quality-adjusted life years gained, costs, and incremental cost-effectiveness ratios. One-way, 2-way, and probabilistic sensitivity analyses were performed. RESULTS: CT angiography and CT perfusion imaging were the dominant strategies, resulting in both better health outcomes and lower costs, even when incorporating brain cancer and cataract risks. Our results remained robust in 2-way sensitivity analyses varying the prolonged latency period up to 30 years, with either brain cancer risk up to 50 times higher than the upper 95% CI limit or the probability of cataracts from 0 to 1. Results were consistent for scenarios that considered either symptomatic or asymptomatic patients with SAH. Probabilistic sensitivity analysis confirmed our findings over a broad range of selected input parameters. CONCLUSIONS: While risks of radiation exposure represent an important consideration, CT angiography and CT perfusion imaging remained the preferred imaging compared with transcranial Doppler sonography in both asymptomatic and symptomatic patients with SAH, with improved health outcomes and lower health care costs, even when modeling a significantly higher risk and shorter latency period for both cataract and brain cancer than that currently known.

Mathematical modelling of scanner-specific bowtie filters for Monte Carlo CT dosimetry.

The purpose of bowtie filters in CT scanners is to homogenize the x-ray intensity measured by the detectors in order to improve the image quality and at the same time to reduce the dose to the patient because of the preferential filtering near the periphery of the fan beam. For CT dosimetry, especially for Monte Carlo calculations of organ and tissue absorbed doses to patients, it is important to take the effect of bowtie filters into account. However, material composition and dimensions of these filters are proprietary. Consequently, a method for bowtie filter simulation independent of access to proprietary data and/or to a specific scanner would be of interest to many researchers involved in CT dosimetry. This study presents such a method based on the weighted computer tomography dose index, CTDIw, defined in two cylindrical PMMA phantoms of 16 cm and 32 cm diameter. With an EGSnrc-based Monte Carlo (MC) code, ratios CTDIw/CTDI100,a were calculated for a specific CT scanner using PMMA bowtie filter models based on sigmoid Boltzmann functions combined with a scanner filter factor (SFF) which is modified during calculations until the calculated MC CTDIw/CTDI100,a matches ratios CTDIw/CTDI100,a, determined by measurements or found in publications for that specific scanner. Once the scanner-specific value for an SFF has been found, the bowtie filter algorithm can be used in any MC code to perform CT dosimetry for that specific scanner. The bowtie filter model proposed here was validated for CTDIw/CTDI100,a considering 11 different CT scanners and for CTDI100,c, CTDI100,p and their ratio considering 4 different CT scanners. Additionally, comparisons were made for lateral dose profiles free in air and using computational anthropomorphic phantoms. CTDIw/CTDI100,a determined with this new method agreed on average within 0.89% (max. 3.4%) and 1.64% (max. 4.5%) with corresponding data published by CTDosimetry (www.impactscan.org) for the CTDI HEAD and BODY phantoms, respectively. Comparison with results calculated using proprietary data for the PHILIPS Brilliance 64 scanner showed agreement on average within 2.5% (max. 5.8%) and with data measured for that scanner within 2.1% (max. 3.7%). Ratios of CTDI100,c/CTDI100, p for this study and corresponding data published by CTDosimetry (www.impactscan.org) agree on average within about 11% (max. 28.6%). Lateral dose profiles calculated with the proposed bowtie filter and with proprietary data agreed within 2% (max. 5.9%), and both calculated data agreed within 5.4% (max. 11.2%) with measured results. Application of the proposed bowtie filter and of the exactly modelled filter to human phantom Monte Carlo calculations show agreement on the average within less than 5% (max. 7.9%) for organ and tissue absorbed doses.

MALT1 is an intrinsic regulator of regulatory T cells.

Regulatory T cells (Tregs) are crucial for the maintenance of immunological self-tolerance and their absence or dysfunction can lead to autoimmunity. However, the molecular pathways that govern Treg biology remain obscure. In this study, we show that the nuclear factor-κB signalling mediator mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is an important novel regulator of both Tregs originating in the thymus ('natural' or nTregs) and Tregs induced to differentiate from naive thymocyte helper (Th) cells in the periphery ('induced' or iTregs). Our examination of mice deficient for MALT1 revealed that these mutants have a reduced number of total Tregs. In young Malt1-/- mice, nTregs are totally absent and iTreg are diminished in the periphery. Interestingly, total Treg numbers increase in older Malt1-/- mice as well as in Malt1-/- mice subjected to experimentally induced inflammation. iTregs isolated from WT and Malt1-/- mice were indistinguishable with respect to their ability to suppress the activities of effector T cells, but Malt1-/- iTregs expressed higher levels of Toll-like receptor (TLR) 2. Treatment of WT and Malt1-/- Th cells in vitro with the TLR2 ligand Pam3Cys strongly enhanced the induction and proliferation of Malt1-/- iTregs. Our data suggest that MALT1 supports nTreg development in the thymus but suppresses iTreg induction in the periphery during inflammation. Our data position MALT1 as a key molecule that contributes to immune tolerance at steady-state while facilitating immune reactivity under stress conditions.

THE DECADE OF THE RABiT (2005-15).

The RABiT (Rapid Automated Biodosimetry Tool) is a dedicated Robotic platform for the automation of cytogenetics-based biodosimetry assays. The RABiT was developed to fulfill the critical requirement for triage following a mass radiological or nuclear event. Starting from well-characterized and accepted assays we developed a custom robotic platform to automate them. We present here a brief historical overview of the RABiT program at Columbia University from its inception in 2005 until the RABiT was dismantled at the end of 2015. The main focus of this paper is to demonstrate how the biological assays drove development of the custom robotic systems and in turn new advances in commercial robotic platforms inspired small modifications in the assays to allow replacing customized robotics with 'off the shelf' systems. Currently, a second-generation, RABiT II, system at Columbia University, consisting of a PerkinElmer cell::explorer, was programmed to perform the RABiT assays and is undergoing testing and optimization studies.

Magnetic resonance elastography identifies fibrosis in adults with alpha-1 antitrypsin deficiency liver disease: a prospective study.

BACKGROUND: Limited data exist on the clinical presentation and non-invasive detection of liver fibrosis in adults with homozygous Z genotype alpha-1 antitrypsin (AAT) deficiency. AIMS: To compare demographic, biochemical, histological and imaging data of AAT deficient patients to normal-control and biopsy-proven non-alcoholic fatty liver disease (NAFLD) patients, and to assess the diagnostic accuracy of magnetic resonance elastography (MRE) in detecting fibrosis in AAT deficiency. METHODS: Study includes 33 participants, 11 per group, who underwent clinical research evaluation, liver biopsy (AAT and NAFLD groups), and MRE. Histological fibrosis was quantified using a modified Ishak 6-point scale and liver stiffness by MRE. Diagnostic performance of MRE in detecting fibrosis was assessed by receiver operating characteristic (ROC) analysis. RESULTS: Mean (±s.d.) of age and BMI of normal-control, AAT and NAFLD groups was 57 (±19), 57 (±18), and 57 (±13) years, and 22.7 (±2.5), 24.8 (±4.0) and 31.0 (±5.1) kg/m(2) respectively. Serum ALT [mean ± s.d.] was similar within normal-control [16.4 ± 4.0] and AAT groups [23.5 ± 10.8], but was significantly lower in AAT than NAFLD even after adjustment for stage of fibrosis (P < 0.05, P = 0.0172). For fibrosis detection, MRE-estimated stiffness had an area under the ROC curve of 0.90 (P < 0.0001); an MRE threshold of ≥3.0 kPa provided 88.9% accuracy, with 80% sensitivity and 100% specificity to detect presence of any fibrosis (stage ≥1). CONCLUSIONS: This pilot prospective study suggests magnetic resonance elastography may be accurate for identifying fibrosis in patients with alpha-1 antitrypsin deficiency. Larger validation studies are warranted.