Two-dimensional UTE overview imaging for dental application.

PURPOSE: To investigate the applicability of a 2D-UTE half-pulse sequence for dental overview imaging and the detection of signal from mineralized dental tissue and caries lesions with ultra-short T2∗ as an efficient alternative to 3D sequences. METHODS: A modified 2D-UTE sequence using 240-µs half-pulses for excitation and a reduction of the coil tune delay from the manufacturer preset value allowed for the acquisition of in vivo dental images with a TE of 35 µs at 1.5T. The common occurrence of out-of-slice signal for half-pulse sequences was avoided by applying a quadratic-phase saturation pulse before each half-RF excitation. A conventional 2D-UTE sequence with a TE of 750 µs, using slice selection rephasing, was used for comparison. RESULTS: Quadratic phase saturation pulses adequately improve the slice profile of half-pulse excitations for dental imaging with a surface coil. In vivo images and SNR measurements show a distinct increase in signal in ultrashort T2∗ tissues for the proposed 2D-UTE half-pulse sequence compared with a 2D-UTE sequence using conventional slice selection, leading to an improved detection of caries lesions. CONCLUSION: The proposed pulse sequence enables the acquisition of in vivo images of a comprehensive overview of bone structures and teeth of a single side of the upper and lower jaw and signal detection from mineralized dental tissues in clinically acceptable scan times.

Multistage three-dimensional UTE lung imaging by image-based self-gating.

PURPOSE: To combine image-based self-gating (img-SG) with ultrashort echo time (UTE) three-dimensional (3D) acquisition for multistage lung imaging during free breathing. METHODS: Three k-space ordering schemes (modified spiral pattern, quasirandom numbers and multidimensional Golden Angle) providing uniform coverage of k-space were investigated for providing low-resolution sliding-window images for image-based respiratory self-gating. The performance of the proposed techniques were compared with the conventional spiral pattern and standard DC-based self-gated methods in volunteers during free breathing. RESULTS: Navigator-like respiratory signals were successfully extracted from the sliding-window data by monitoring the lung-liver interface displacement. A temporal resolution of 588 ms was adequate to retrieve gating signals from the lung-liver interface. Images reconstructed with the img-SG technique showed significantly better sharpness and apparent diaphragm excursion than any of the DC-SG methods. Direct comparison of the three implemented ordering schemes did not demonstrate any clear superiority of one with respect to the others. CONCLUSION: Image-based respiratory self gating in UTE 3D lung images allows successful retrospective respiratory gating, also enabling reconstruction of intermediate respiratory stages.

Self-gated tissue phase mapping using golden angle radial sparse SENSE.

PURPOSE: To investigate the combination of Golden Angle Radial Sparse SENSE reconstruction with image-based self-gating (SG) for deriving high-quality TPM data from radial golden angle (GA) k-space data. METHODS: In 10 healthy volunteers, a self-gated radial GA TPM sequence (TPMSG ) was compared with a prospectively triggered radial TPM acquisition with conventional respiratory (RNAV) compensation (TPMref ). Image quality and velocities were compared for different regularization strengths λ in the CS reconstruction. RESULTS: Acquisitions and retrospective self-gating was successful in all cases. Contrast in TPMSG was superior to TPMref , because the blood saturation bands could be applied with full thickness without interference with the RNAV. Velocities from both acquisitions visually showed the same motion patterns and were quantitatively highly similar (correlation 0.81-0.97 and RMSE 0.08-0.21 cm/s). Strong temporal regularization ( λ∈0.3,0.4) led to reduced velocity peaks in TPMSG . For λ=0.2, image sharpness as well as velocity peaks of TPMSG were comparable to TPMRef . CONCLUSION: The combination of Golden Angle Radial Sparse SENSE with image-based self-gating allows measurement of velocities of the myocardium with superior black-blood contrast and full coverage of the cardiac cycle.

A self-gating method for time-resolved imaging of nonuniform motion.

PURPOSE: To develop a self-gating method capable of assessing nonuniform motion, e.g., in cardiovascular magnetic resonance imaging of patients with severe arrhythmia, or for imaging of the temporomandibular joint. METHODS: The proposed method allows cyclic motion trajectories with a nonuniform pace by replacing the one-dimensional gating signal of conventional image-based self-gating with a two-dimensional gating matrix. The resulting image quality is compared with conventional self-gating and real-time MRI. RESULTS: Nonuniform self-gating resulted in superior image quality compared with conventional self-gating and the feasibility study showed significantly improved image sharpness (P < 0.01). Further, improvements in image quality were shown compared with golden angle radial parallel sparse MRI. CONCLUSION: A new self-gating method was proposed that allows cardiovascular magnetic resonance of arrhythmic patients, which is a common problem in clinical practice. Further, the proposed method enables self-gated imaging of the temporomandibular joint. Magn Reson Med 76:919-925, 2016. © 2015 Wiley Periodicals, Inc.

Golden ratio sparse MRI using tiny golden angles.

PURPOSE: The combination of fully balanced SSFP sequences with iterative golden angle radial sparse parallel (iGRASP) MRI leads to strong image artifacts due to eddy currents caused by the large angular increment of the golden angle ordering. The purpose of this work is to enable the combination of iterative golden angle radial sparse parallel MRI with balanced SSFP using the recently presented tiny golden angles. METHODS: The tiny golden angle trajectories are analyzed for their incoherence properties in relation to sparse imaging using the time-resolved point-spread functions. Tiny golden angle radial sparse parallel (tyGRASP) MRI is introduced and evaluated with applications in cardiac imaging and dynamic imaging of the temporomandibular joint. The results are analyzed in detail for 3 T and verified for 1.5 T. RESULTS: The incoherence properties of the tiny golden angle trajectory are comparable to the incoherence properties of the golden angle trajectory and are well suited for sparse MRI reconstruction. The proposed tiny golden angle radial sparse parallel MRI method strongly reduces eddy current related artifacts for both applications. CONCLUSION: This work enables sparse, golden-ratio-based imaging with balanced SSFP sequences. Magn Reson Med 75:2372-2378, 2016. © 2015 Wiley Periodicals, Inc.

On the influence of respiratory motion in radial tissue phase mapping cardiac MRI.

PURPOSE: To investigate the impact of respiratory motion on radial tissue phase mapping (TPM) measurements, and to improve image quality and scan efficiency without compromising velocity fidelity by increasing the respiratory acceptance window with and without motion correction. MATERIALS AND METHODS: A radial golden angle TPM sequence was measured in 10 healthy volunteers in three short axis slices at 3T. Ungated ( CFREE), self-gated with a single acceptance window ( CREF), motion-corrected averaging using all ( CMCall), or selected ( CMC) data reconstructions were compared by means of various image quality measures and resulting velocities. RESULTS: Using all data ( CFREE) resulted in significantly higher perceived signal-to-noise ratio (SNR) (P < 0.001), but significantly reduced sharpness (P < 0.001) and contrast (P = 0.02), when compared to CREF. Coefficient of variation (CV) and perceived sharpness were not significantly different (P > 0.05). With motion-correction, perceived sharpness could be significantly improved ( CMC: P = 0.002; CMCall: P = 0.002) in comparison to CFREE. Velocity peaks of CFREE were significantly reduced compared to CREF (all peaks: P < 0.001; except the longitudinal "E" peak: P = 0.03). The peak velocities in CMC and CMCall were not significantly different from CREF (all peaks: P > 0.08; except longitudinal "E"/"A" peaks: P > 0.01). CONCLUSION: Free-breathing reconstruction results in good perceived image sharpness and velocity information with slightly, but significantly, reduced peak velocities. For achieving velocities and image quality comparable to data from a single acceptance window, but higher gating efficiency, selected motion-corrected TPM (CMC) can be applied. J. Magn. Reson. Imaging 2016;44:1218-1228.

High-resolution respiratory self-gated golden angle cardiac MRI: Comparison of self-gating methods in combination with k-t SPARSE SENSE.

PURPOSE: To compare the applicability of different self-gating (SG) strategies for respiratory SG in cardiac MRI in combination with iteratively reconstructed (k-t SPARSE SENSE) cine data with low and high temporal resolution. METHODS: Eleven SG variants were compared in five volunteers by assessment of the resulting image sharpness compared with nongated reconstructions. Promising SG techniques were applied for high temporal resolution reconstructions of the heart function. RESULTS: SG was successful in all volunteers with image-based SG and the ∑||p|| technique. These approaches were also superior to gating from the respiratory bellows signal on average. Combination with k-t SPARSE SENSE enabled high temporally resolved visualization of the heart motion with free breathing. CONCLUSION: Respiratory SG can be applied for improving image sharpness. Combining SG with iterative reconstruction allows generation of high temporal resolution cine data, which reveal more details of cardiac motion.

Combination of tagging and tissue phase mapping to accelerate myocardial motion measurements in three directions.

OBJECT: Until now, a three-directional velocity field has mostly been obtained by velocity encoding in three directions, which is very time-consuming and hence not usually used in clinical routine. We show the feasibility of combining in-plane tagging with through-plane tissue phase mapping (TPM) to encode a three-directional velocity field at 3 T with reduced overall acquisition time. MATERIALS AND METHODS: Assessment of a three-directional velocity field was performed for 10 healthy volunteers. The motion patterns obtained by use of five different sequences including three-directional TPM, TPM in the through-plane direction, TPM in the through-plane direction with horizontal or vertical tagging lines, and TPM in the through-plane direction combined with a tagging grid were evaluated and compared. RESULTS: A three-dimensional velocity field can be obtained in approximately half the acquisition time by combining through-plane TPM with in-plane tagging. Although the velocity information is derived by different means, differences between the information obtained by three-directional TPM encoding and the suggested technique are only minor. CONCLUSION: The combination of tagging and TPM enables assessment of the three-directional velocity field in nearly half the time taken when the conventional three-directional TPM sequence is used.

Volumetric motion quantification by 3D tissue phase mapped CMR.

BACKGROUND: The objective of this study was the quantification of myocardial motion from 3D tissue phase mapped (TPM) CMR. Recent work on myocardial motion quantification by TPM has been focussed on multi-slice 2D acquisitions thus excluding motion information from large regions of the left ventricle. Volumetric motion assessment appears an important next step towards the understanding of the volumetric myocardial motion and hence may further improve diagnosis and treatments in patients with myocardial motion abnormalities. METHODS: Volumetric motion quantification of the complete left ventricle was performed in 12 healthy volunteers and two patients applying a black-blood 3D TPM sequence. The resulting motion field was analysed regarding motion pattern differences between apical and basal locations as well as for asynchronous motion pattern between different myocardial segments in one or more slices. Motion quantification included velocity, torsion, rotation angle and strain derived parameters. RESULTS: All investigated motion quantification parameters could be calculated from the 3D-TPM data. Parameters quantifying hypokinetic or asynchronous motion demonstrated differences between motion impaired and healthy myocardium. CONCLUSIONS: 3D-TPM enables the gapless volumetric quantification of motion abnormalities of the left ventricle, which can be applied in future application as additional information to provide a more detailed analysis of the left ventricular function.

AFM13 in patients with relapsed or refractory classical Hodgkin lymphoma: final results of an open-label, randomized, multicenter phase II trial.

In patients with relapse of classical Hodgkin lymphoma (cHL) after autologous stem cell transplant, brentuximab vedotin and anti-PD1 treatment, the outcome is poor. To assess the efficacy of the bispecific anti-CD30/CD16A, NK-cell engaging antibody AFM13 and to select the optimal treatment schedule (arm A-C), we initiated a randomized two-stage phase II trial (NCT02321592). Due to slow recruitment, the trial was terminated after treatment of 25 patients. Treatment with AFM13 was well tolerated: only two treatment-associated serious adverse events (SAEs) were reported; all SAEs resolved completely. With an objective response rate (ORR) of 16.7% (1/5 in arm A, 1/11 in arm B, and 2/8 in arm C) and a 12-month progression-free survival (PFS) of 12.6% (95% CI 3.2-28.9), treatment efficacy of AFM13 monotherapy in all evaluable patients was modest. The continuous application schedule (arm C) might be more effective, but the visit schedule should be better aligned with patients' daily life.

Left ventricular myocardial strain quantification with two- and three-dimensional cardiovascular magnetic resonance based tissue tracking.

BACKGROUND: Cardiovascular magnetic resonance based tissue tracking (CMR-TT) was reported to provide detailed insight into left ventricular (LV) contractile function and deformation with both of two- and three-dimensional (2/3D) algorithms. This study was designed to investigate the feasibility and reproducibility of these two techniques for measuring LV global and segmental strain, and establish gender- and age-related reference values of global multi-dimensional peak strains among large healthy population. METHODS: We retrospectively recruited 150 healthy volunteers (75 males/females) and divided them into three age groups (G20-40, G41-60 and G61-80). LV global mean and peak strains as well as segmental strains in radial, circumferential and longitudinal directions were derived from post-hoc 2/3D CMR-TT analysis of standard steady-state free precession (SSFP) cine images acquired at 1.5T field strength. RESULTS: Both 2D and 3D CMR-TT modalities enable the tracking of LV myocardial tissues and generate global and segmental strain data. By comparison, 3D CMR-TT was more feasible in measuring segmental deformation since it could generate values at all segments. The amplitudes of LV 3D global peak strain were the smallest among those of 2/3D corresponding global mean or peak strains except in the radial direction, and was highly correlated with 2D global mean strains (correlation coefficient r=0.71-0.90), 2D global peak strains (r=0.75-0.89) and 3D global mean strains (all r=0.99). In healthy cohort, LV 3D global peak values were 44.4%±13.0% for radial, -17.0%±2.7% for circumferential and -15.4%±2.3% for longitudinal strain. Females showed significantly larger amplitude of strains than males, especially in G61-80 (P<0.05). The subjects in G61-80 showed larger amplitude of strains than the volunteers in younger groups. The intra- and inter-observer agreement of 2/3D CMR-TT analysis in evaluating LV myocardial global deformation was better than segmental measurement. CONCLUSIONS: CMR-TT is a feasible and reproducible technique for assessing LV myocardial deformation, especially at the global level. The establishment of specific reference values of LV global and segmental systolic strains and the investigation of dimension-, gender- and age-related differences provide a fundamental insight into the features of LV contraction and works as an essential step in clinical routine.

A Signal Acquisition Setup for Ultrashort Echo Time Imaging Operating in Parallel on Unmodified Clinical MRI Scanners Achieving an Acquisition Delay of [Formula: see text].

Ultrashort echo time imaging on clinical systems is still limited by the rather long radio frequency switching times achievable with standard front end concepts. In this contribution, an independent parallel receive-only system is interfaced to an unmodified clinical MRI system, enabling imaging of species with ultrashort relaxation times, such as bone, tendon, teeth, or lung tissue. Synchronization of the system is achieved by an electronically decoupled one-way trigger line, a clock reference signal, and RF pulse tracking, thus ensuring minimal interference with the host system. With the proposed system, an acquisition delay of [Formula: see text] is experimentally demonstrated.

Pretreatment Vitamin D Deficiency Is Associated With Impaired Progression-Free and Overall Survival in Hodgkin Lymphoma.

PURPOSE: Vitamin D deficiency is described as a modifiable risk factor for the incidence of and mortality in many common cancers; however, data in Hodgkin lymphoma (HL) are lacking. PATIENTS AND METHODS: We thus performed a study measuring pretreatment vitamin D levels in prospectively treated patients with HL and correlated this with clinical outcomes. A total of 351 patients from the German Hodgkin Study Group clinical trials (HD7, HD8, and HD9) were included. RESULTS: Fifty percent of patients were vitamin D deficient (< 30 nmol/L) before planned chemotherapy. Pretreatment vitamin D deficiency was more common in relapsed/refractory patients than matched relapse-free controls (median baseline vitamin D, 21.4 nmol/L v 35.5 nmol/L; proportion with vitamin D deficiency, 68% v 41%; P < .001). Vitamin D-deficient patients had impaired progression-free survival (10-year difference, 17.6%; 95% CI, 6.9% to 28.4%; hazard ratio, 2.13; 95% CI, 1.84 to 2.48; P < .001) and overall survival (10-year difference, 11.1%; 95% CI, 2.1% to 20.2%; hazard ratio, 1.82; 95% CI, 1.53 to 2.15; P < .001), consistent across trials and treatment groups. We demonstrated that vitamin D status is an independent predictor of outcome and hypothesized that vitamin D status might be important for the chemosensitivity of HL. We subsequently performed experiments supplementing physiologic doses of vitamin D (calcitriol) to cultured HL cell lines and demonstrated increased antiproliferative effects in combination with chemotherapy. In an HL-xenograft animal model, we showed that supplemental vitamin D (dietary supplement, cholecalciferol) improves the chemosensitivity of tumors by reducing the rate of tumor growth compared with vitamin D or chemotherapy alone. CONCLUSION: On the basis of our clinical and preclinical findings, we encourage that vitamin D screening and replacement be incorporated into future randomized clinical trials to properly clarify the role of vitamin D replacement therapy in HL.

Development of a human mitochondrial oligonucleotide microarray (h-MitoArray) and gene expression analysis of fibroblast cell lines from 13 patients with isolated F1Fo ATP synthase deficiency.

BACKGROUND: To strengthen research and differential diagnostics of mitochondrial disorders, we constructed and validated an oligonucleotide microarray (h-MitoArray) allowing expression analysis of 1632 human genes involved in mitochondrial biology, cell cycle regulation, signal transduction and apoptosis. Using h-MitoArray we analyzed gene expression profiles in 9 control and 13 fibroblast cell lines from patients with F1Fo ATP synthase deficiency consisting of 2 patients with mt9205deltaTA microdeletion and a genetically heterogeneous group of 11 patients with not yet characterized nuclear defects. Analysing gene expression profiles, we attempted to classify patients into expected defect specific subgroups, and subsequently reveal group specific compensatory changes, identify potential phenotype causing pathways and define candidate disease causing genes. RESULTS: Molecular studies, in combination with unsupervised clustering methods, defined three subgroups of patient cell lines--M group with mtDNA mutation and N1 and N2 groups with nuclear defect. Comparison of expression profiles and functional annotation, gene enrichment and pathway analyses of differentially expressed genes revealed in the M group a transcription profile suggestive of synchronized suppression of mitochondrial biogenesis and G1/S arrest. The N1 group showed elevated expression of complex I and reduced expression of complexes III, V, and V-type ATP synthase subunit genes, reduced expression of genes involved in phosphorylation dependent signaling along MAPK, Jak-STAT, JNK, and p38 MAP kinase pathways, signs of activated apoptosis and oxidative stress resembling phenotype of premature senescent fibroblasts. No specific functionally meaningful changes, except of signs of activated apoptosis, were detected in the N2 group. Evaluation of individual gene expression profiles confirmed already known ATP6/ATP8 defect in patients from the M group and indicated several candidate disease causing genes for nuclear defects. CONCLUSION: Our analysis showed that deficiency in the ATP synthase protein complex amount is generally accompanied by only minor changes in expression of ATP synthase related genes. It also suggested that the site (mtDNA vs nuclear DNA) and the severity (ATP synthase content) of the underlying defect have diverse effects on cellular gene expression phenotypes, which warrants further investigation of cell cycle regulatory and signal transduction pathways in other OXPHOS disorders and related pharmacological models.

Quasi-Random Single-Point Imaging Using Low-Discrepancy $k$ -Space Sampling.

Magnetic resonance imaging of short relaxation time spin systems has been a widely discussed topic with serious clinical applications and led to the emergence of fast imaging ultra-short echo-time sequences. Nevertheless, these sequences suffer from image blurring, due to the related sampling point spread function and are highly prone to imaging artefacts arising from, e.g., chemical shifts or magnetic susceptibilities. In this paper, we present a concept of spherical quasi-random single-point imaging. The approach is highly accelerateable, due to intrinsic undersampling properties and capable of strong metal artefact suppression. Imaging acceleration is achieved by sampling of quasi-random points in -space, based on a low-discrepancy sequence, and a combination with non-linear optimization reconstruction techniques [compressed sensing (CS)]. The presented low-discrepancy trajectory shows ideal noise like undersampling properties for the combination with CS, leading to denoised images with excellent metal artefact reduction. Using eightfold undersampling, acquisition time of a few minutes can be achieved for volume acquisitions.

Workplace disaster preparedness and response: the employee assistance program continuum of services.

Response programs for workplace critical and traumatic events are becoming an acknowledged and sought after standard of care. The current trauma literature recognizes what goes on in the workplace between the Employee Assistance Program (EAP) and management. The authors have taken this intra-organizational relationship, assimilated the information, and developed a model that recognizes and supports management throughout the continuum of response to workplace traumatic events. The model recognizes the EAP as an important workplace resource and tool in management's ability to strike the balance of managing the workforce while assisting in recovery following workplace trauma. The introduced concept defines the continuum and highlights the before, during, and after phases, showing how EAP supports management in most effectively doing their job.

A Small Surrogate for the Golden Angle in Time-Resolved Radial MRI Based on Generalized Fibonacci Sequences.

In golden angle radial magnetic resonance imaging a constant azimuthal radial profile spacing of 111.246...(°) guarantees a nearly uniform azimuthal profile distribution in k-space for an arbitrary number of radial profiles. Even though this profile order is advantageous for various real-time imaging methods, in combination with balanced steady-state free precession (SSFP) sequences the large azimuthal angle increment may lead to strong image artifacts, due to the varying eddy currents introduced by the rapidly switching gradient scheme. Based on a generalized Fibonacci sequence, a new sequence of smaller irrational angles is introduced ( 49.750...(°), 32.039...(°), 27.198...(°), 23.628...(°), ... ). The subsequent profile orders guarantee the same sampling efficiency as the golden angle if at least a minimum number of radial profiles is used for reconstruction. The suggested angular increments are applied for dynamic imaging of the heart and the temporomandibular joint. It is shown that for balanced SSFP sequences, trajectories using the smaller golden angle surrogates strongly reduce the image artifacts, while the free retrospective choice of the reconstruction window width is maintained.

Differential expression of ATPAF1 and ATPAF2 genes encoding F(1)-ATPase assembly proteins in mouse tissues.

Atp11p (Atpaf1p; F(1)-ATPase assembly factor 1) and Atp12p (Atpaf2p; F(1)-ATPase assembly factor 2) are proteins required for the assembly of beta (F(1)-beta) and alpha (F(1)-alpha) subunits into the mitochondrial ATPase. Here we report about 100 times lower levels of ATPAF1 and ATPAF2 transcripts in relation to the mRNA levels of F(1)-alpha and F(1)-beta in a range of mouse tissues. Quantitative reverse-transcription polymerase chain reaction revealed nearly constant ATPAF1 expression in all tissues in both adult and 5-day-old mice (up to two-fold differences), indicating that ATPAF1 rather behaves like a maintenance gene. In contrast, ATPAF2 expression differed up to 30-fold in the tissues analysed. ATPAF2 tissue-specific expression was also found to correlate well with mRNA levels of both F(1)-alpha and F(1)-beta (BATz.Gt;kidney, liver>heart, brain>skeletal muscle), showing the highest mRNA level in the thermogenic, ATPase-poor brown adipose tissue, which is characterised by a 10-fold decrease in ATPase/respiratory chain stoichiometry relative to the other tissues.

Bovine carbonyl lactoperoxidase structure at 2.0Å resolution and infrared spectra as a function of pH.

Lactoperoxidase (LPO) is a hemeprotein catalyzing the oxidation of thiocyanate and I(-) into antimicrobials and small aromatic organics after being itself oxidized by H(2)O(2). LPO is excreted by the lungs, mammary glands, found in saliva and tears and protects mammals against bacterial, fungal and viral invasion. The Fe(II) form binds CO which inactivates LPO like many other hemeproteins. We present the 3-dimensional structure of CO-LPO at 2.0Å resolution and infrared (IR) spectra of the iron-bound CO stretch from pH 3 to 8.8 at 1 cm(-1) resolution. The observed Fe-C-O bond angle of 132° is more acute than the electronically related Fe(III), CN-LPO with a Fe-C-N angle of 161°. The orientations of the two ligands are different with the oxygen of CO pointing towards the imidazole of distal His109 while the nitrogen of CN points away, the Fe(II) moves towards His109 while the Fe(III) moves away; both movements are consistent with a hydrogen bond between the distal His109 and CO, but not to the nitrogen of CN-LPO. The IR spectra of CO-LPO exhibit two major CO absorbances with pH dependent relative intensities. Both crystallographic and IR data suggest proton donation to the CO oxygen by His109 with a pK ≈ 4; close to the pH of greatest enzyme turnover. The IR absorbance maxima are consistent with a first order correlation between frequency and Fe(III)/Fe(II) reduction potential at pH 7; both band widths at half-height correlate with electron density donation from Fe(II) to CO as gauged by the reduction potential.

Lower serum paraoxonase-1 activity is related to higher serum amyloid a levels in metabolic syndrome.

BACKGROUND AND AIMS: High-density lipoproteins (HDL) contain the anti-oxidative enzyme, paraoxonase-1 (PON-1), which is important for atheroprotection. The acute phase reactant, serum amyloid A (SAA), an HDL-associated apolipoprotein, may impair PON-1 activity, whereas SAA and PON-1 are reciprocally regulated in response to acute inflammatory stimuli. The relationship of serum PON-1 activity with SAA during low-grade chronic inflammation is unclear. Here we tested the extent to which low serum PON-1 activity is related to high SAA levels in subjects with and without metabolic syndrome (MetS). METHODS: In 19 nondiabetic subjects with MetS and 67 subjects without MetS, serum PON-1, assayed as its arylesterase activity, and SAA were measured together with plasma lipids and lipoproteins, high-sensitive C-reactive protein (hs-CRP) and insulin resistance (homeostasis model assessment (HOMA(ir)). RESULTS: PON-1 activity was decreased (p=0.023), whereas SAA levels were increased (p=0.042) in MetS subjects, coinciding with higher hs-CRP levels and HOMA(ir) values. Multiple linear regression analysis revealed that age- and gender-adjusted PON-1 activity was related inversely to SAA (ß=-0.256, p=0.020) after adjustment for MetS, or alternatively for hs-CRP and HOMA(ir) (ß=-0.271, p=0.049). CONCLUSIONS: Decreased serum PON-1 activity in MetS may in part be attributable to higher SAA levels. We suggest that higher SAA levels contribute to impaired HDL anti-oxidative function in MetS via an effect on PON-1 regulation.