Monocyte MRI Relaxation Rates Are Regulated by Extracellular Iron and Hepcidin.

Many chronic inflammatory conditions are mediated by an increase in the number of monocytes in peripheral circulation, differentiation of monocytes to macrophages, and different macrophage subpopulations during pro- and anti-inflammatory stages of tissue injury. When hepcidin secretion is stimulated during inflammation, the iron export protein ferroportin is targeted for degradation on a limited number of cell types, including monocytes and macrophages. Such changes in monocyte iron metabolism raise the possibility of non-invasively tracking the activity of these immune cells using magnetic resonance imaging (MRI). We hypothesized that hepcidin-mediated changes in monocyte iron regulation influence both cellular iron content and MRI relaxation rates. In response to varying conditions of extracellular iron supplementation, ferroportin protein levels in human THP-1 monocytes decreased two- to eightfold, consistent with paracrine/autocrine regulation of iron export. Following hepcidin treatment, ferroportin protein levels further decreased two- to fourfold. This was accompanied by an approximately twofold increase in total transverse relaxation rate, R2*, compared to non-supplemented cells. A positive correlation between total cellular iron content and R2* improved from moderate to strong in the presence of hepcidin. These findings suggest that hepcidin-mediated changes detected in monocytes using MRI could be valuable for in vivo cell tracking of inflammatory responses.

The Effect of Registration on Voxel-Wise Tofts Model Parameters and Uncertainties from DCE-MRI of Early-Stage Breast Cancer Patients Using 3DSlicer.

We quantitatively investigate the influence of image registration, using open-source software (3DSlicer), on kinetic analysis (Tofts model) of dynamic contrast enhanced MRI of early-stage breast cancer patients. We also show that registration computation time can be reduced by reducing the percent sampling (PS) of voxels used for estimation of the cost function. DCE-MRI breast images were acquired on a 3T-PET/MRI system in 13 patients with early-stage breast cancer who were scanned in a prone radiotherapy position. Images were registered using a BSpline transformation with a 2 cm isotropic grid at 100, 20, 5, 1, and 0.5PS (BRAINSFit in 3DSlicer). Signal enhancement curves were analyzed voxel-by-voxel using the Tofts kinetic model. Comparing unregistered with registered groups, we found a significant change in the 90th percentile of the voxel-wise distribution of Ktrans. We also found a significant reduction in the following: (1) in the standard error (uncertainty) of the parameter value estimation, (2) the number of voxel fits providing unphysical values for the extracellular-extravascular volume fraction (ve > 1), and (3) goodness of fit. We found no significant differences in the median of parameter value distributions (Ktrans, ve) between unregistered and registered images. Differences between parameters and uncertainties obtained using 100PS versus 20PS were small and statistically insignificant. As such, computation time can be reduced by a factor of 2, on average, by using 20PS while not affecting the kinetic fit. The methods outlined here are important for studies including a large number of post-contrast images or number of patient images.

MRI T2 and T1ρ relaxation in patients at risk for knee osteoarthritis: a systematic review and meta-analysis.

BACKGROUND: Magnetic resonance imaging (MRI) T2 and T1ρ relaxation are increasingly being proposed as imaging biomarkers potentially capable of detecting biochemical changes in articular cartilage before structural changes are evident. We aimed to: 1) summarize MRI methods of published studies investigating T2 and T1ρ relaxation time in participants at risk for but without radiographic knee OA; and 2) compare T2 and T1ρ relaxation between participants at-risk for knee OA and healthy controls. METHODS: We conducted a systematic review of studies reporting T2 and T1ρ relaxation data that included both participants at risk for knee OA and healthy controls. Participant characteristics, MRI methodology, and T1ρ and T2 relaxation data were extracted. Standardized mean differences (SMDs) were calculated within each study. Pooled effect sizes were then calculated for six commonly segmented knee compartments. RESULTS: 55 articles met eligibility criteria. There was considerable variability between scanners, coils, software, scanning protocols, pulse sequences, and post-processing. Moderate risk of bias due to lack of blinding was common. Pooled effect sizes indicated participants at risk for knee OA had lengthened T2 relaxation time in all compartments (SMDs from 0.33 to 0.74; p < 0.01) and lengthened T1ρ relaxation time in the femoral compartments (SMD from 0.35 to 0.40; p < 0.001). CONCLUSIONS: T2 and T1ρ relaxation distinguish participants at risk for knee OA from healthy controls. Greater standardization of MRI methods is both warranted and required for progress towards biomarker validation.

Investigating the Relationship between Transverse Relaxation Rate (R2) and Interecho Time in MagA-Expressing, Iron-Labeled Cells.

Reporter gene-based labeling of cells with iron is an emerging method of providing magnetic resonance imaging contrast for long-term cell tracking and monitoring cellular activities. This report investigates 9.4 T nuclear magnetic resonance properties of mammalian cells overexpressing MagA, a putative iron transport protein from magnetotactic bacteria. MagA-expressing MDA-MB-435 cells were cultured in the presence and absence of iron supplementation and compared to the untransfected control. The relationship between the transverse relaxation rate (R2) and interecho time was investigated using the Carr-Purcell-Meiboom-Gill sequence. This relationship was analyzed using a model based on water diffusion in weak magnetic field inhomogeneities (Jensen-Chandra model) as well as a fast-exchange model (Luz-Meiboom model). Increases in R2 with increasing interecho time were larger in the iron-supplemented, MagA-expressing cells compared to other cells. The dependence of R2 on interecho time in these iron-supplemented, MagA-expressing cells was better represented by the Jensen-Chandra model compared to the Luz-Meiboom model, whereas the Luz-Meiboom model performed better for the remaining cell types. Our findings provide an estimate of the distance scale of microscopic magnetic field variations in MagA-expressing cells, which is thought to be related to the size of iron-containing vesicles.

Essential magnetosome proteins MamI and MamL from magnetotactic bacteria interact in mammalian cells.

To detect cellular activities deep within the body using magnetic resonance platforms, magnetosomes are the ideal model of genetically-encoded nanoparticles. These membrane-bound iron biominerals produced by magnetotactic bacteria are highly regulated by approximately 30 genes; however, the number of magnetosome genes that are essential and/or constitute the root structure upon which biominerals form is largely undefined. To examine the possibility that key magnetosome genes may interact in a foreign environment, we expressed mamI and mamL as fluorescent fusion proteins in mammalian cells. Localization and potential protein-protein interaction(s) were investigated using confocal microscopy and fluorescence correlation spectroscopy (FCS). Enhanced green fluorescent protein (EGFP)-MamI and the red fluorescent Tomato-MamL displayed distinct intracellular localization, with net-like and punctate fluorescence, respectively. Remarkably, co-expression revealed co-localization of both fluorescent fusion proteins in the same punctate pattern. An interaction between MamI and MamL was confirmed by co-immunoprecipitation. In addition, changes in EGFP-MamI distribution were accompanied by acquisition of intracellular mobility which all Tomato-MamL structures displayed. Analysis of extracts from these cells by FCS was consistent with an interaction between fluorescent fusion proteins, including an increase in particle radius. Co-localization and interaction of MamI and MamL demonstrate that select magnetosome proteins may associate in mammalian cells.

Bacterial association with metals enables in vivo monitoring of urogenital microbiota using magnetic resonance imaging.

Bacteria constitute a significant part of the biomass of the human microbiota, but their interactions are complex and difficult to replicate outside the host. Exploiting the superior resolution of magnetic resonance imaging (MRI) to examine signal parameters of selected human isolates may allow tracking of their dispersion throughout the body. Here we investigate longitudinal and transverse MRI relaxation rates and found significant differences between several bacterial strains. Common commensal strains of lactobacilli display notably high MRI relaxation rates, partially explained by elevated cellular manganese content, while other species contain more iron than manganese. Lactobacillus crispatus show particularly high values, 4-fold greater than any other species; up to 60-fold greater signal than relevant tissue background; and a linear relationship between relaxation rate and fraction of live cells. Different bacterial strains have detectable, repeatable MRI relaxation rates that in the future may enable monitoring of their persistence in the human body for enhanced molecular imaging.

Improved PET/MRI accuracy by use of static transmission source in empirically derived hardware attenuation correction.

BACKGROUND: Accurate quantification of radioactivity, measured by an integrated positron emission tomography (PET) and magnetic resonance imaging (MRI) system, is still a challenge. One aspect of such a challenge is to correct for the hardware attenuation, such as the patient table and radio frequency (RF) resonators. For PET/MRI systems, computed tomography (CT) is commonly used to produce hardware attenuation correction (AC) maps, by converting Hounsfield units (HU) to a linear attenuation coefficients (LAC) map at the PET energy level 511 keV, using a bilinear model. The model does not address beam hardening, nor higher density materials, which can lead to inaccurate corrections. PURPOSE: In this study, we introduce a transmission-based (TX-based) AC technique with a static Germanium-68 (Ge-68) transmission source to generate hardware AC maps using the PET/MRI system itself, without the need for PET or medical CT scanners. The AC TX-based maps were generated for a homogeneous cylinder, made of acrylic as a validator. The technique thereafter was applied to the patient table and posterior part of an RF-phased array used in cardiovascular PET/MRI imaging. The proposed TX-based, and the CT-based, hardware maps were used in reconstructing PET images of one cardiac patient, and the results were analysed and compared. RESULTS: The LAC derived by the TX-based method for the acrylic cylinder is estimated to be 0.10851 ± 0.00380 cm-1 compared to the 0.10698 ± 0.00321 cm-1 theoretical value reported in the literature. The PET photon counts were reduced by 8.7 ± 1.1% with the patient table, at the region used in cardiac scans, while the CT-based map, used for correction, over-estimated counts by 4.3 ± 1.3%. Reconstructed in vivo images using TX-based AC hardware maps have shown 4.1 ± 0.9% mean difference compared to those reconstructed images using CT-based AC. CONCLUSIONS: The LAC of the acrylic cylinder measurements using the TX-based technique was in agreement with those in the literature confirming the validity of the technique. The over-estimation of photon counts caused by the CT-based model used for the patient table was improved by the TX-based technique. Therefore, TX-based AC of hardware using the PET/MRI system itself is possible and can produce more accurate images when compared to the CT-based hardware AC in cardiac PET images.

Intrafraction motion monitoring to determine PTV margins in early stage breast cancer patients receiving neoadjuvant partial breast SABR.

BACKGROUND AND PURPOSE: To quantify intra-fraction tumor motion using imageguidance and implanted fiducial markers to determine if a 5 mm planning-target-volume (PTV) margin is sufficient for early stage breast cancer patients receiving neoadjuvant stereotactic ablative radiotherapy (SABR). MATERIALS AND METHODS: A HydroMark© (Mammotome) fiducial was implanted at the time of biopsy adjacent to the tumor. Sixty-one patients with 62 tumours were treated prone using a 5 mm PTV margin. Motion was quantified using two methods (separate patient groups): 1) difference in 3D fiducial position pre- and post-treatment cone-beam CTs (CBCTs) in 18 patients receiving 21 Gy/1fraction (fx); 2) acquiring 2D triggered-kVimages to quantify 3D intra-fraction motion using a 2D-to-3D estimation method for 44 tumours receiving 21 Gy/1fx (n = 22) or 30 Gy/3fx (n = 22). For 2), motion was quantified by calculating the magnitude of intra-fraction positional deviation from the pretreatment CBCT. PTV margins were derived using van Herkian analysis. RESULTS: The average ± standard deviation magnitude of motion across patients was 1.3 ± 1.15 mm Left/Right (L/R), 1.0 ± 0.9 mm Inferiorly/Superiorly (I/S), and 1.8 ± 1.5 mm Anteriorly/Posteriorly (A/P). 85/105 (81%) treatment fractions had dominant anterior motion. 6/62patients (9.7%) had mean intra-fraction motion during any fraction > 5 mm in any direction, with 4 in the anterior direction. Estimated PTV margins for single and three-fx patients in the L/R, I/S, and A/P directions were 6.0x4.1x5.9 mm and 4.5x2.9x4.3 mm, respectively. CONCLUSION: Our results suggest that a 5 mm PTV margin is sufficient for the I/S and A/P directions if a lateral kV image is acquired immediately before treatment. For the L/R direction, either further immobilization or a larger margin is required.

An evaluation of the diagnostic equivalence of 18F-FDG-PET between hybrid PET/MRI and PET/CT in drug-resistant epilepsy: A pilot study.

OBJECTIVE: Hybrid PET/MRI may improve detection of seizure-onset zone (SOZ) in drug-resistant epilepsy (DRE), however, concerns over PET bias from MRI-based attenuation correction (MRAC) have limited clinical adoption of PET/MRI. This study evaluated the diagnostic equivalency and potential clinical value of PET/MRI against PET/CT in DRE. MATERIALS AND METHODS: MRI, FDG-PET and CT images (n = 18) were acquired using a hybrid PET/MRI and a CT scanner. To assess diagnostic equivalency, PET was reconstructed using MRAC (RESOLUTE) and CT-based attenuation correction (CTAC) to generate PET/MRI and PET/CT images, respectively. PET/MRI and PET/CT images were compared qualitatively through visual assessment and quantitatively through regional standardized uptake value (SUV) and z-score assessment. Diagnostic accuracy and sensitivity of PET/MRI and PET/CT for SOZ detection were calculated through comparison to reference standards (clinical hypothesis and histopathology, respectively). RESULTS: Inter-reader agreement in visual assessment of PET/MRI and PET/CT images was 78 % and 81 %, respectively. PET/MRI and PET/CT were strongly correlated in mean SUV (r = 0.99, p < 0.001) and z-scores (r = 0.92, p < 0.001) across all brain regions. MRAC SUV bias was <5% in most brain regions except the inferior temporal gyrus, temporal pole, and cerebellum. Diagnostic accuracy and sensitivity were similar between PET/MRI and PET/CT (87 % vs. 85 % and 83 % vs. 83 %, respectively). CONCLUSION: We demonstrate here that PET/MRI with optimal MRAC can yield similar diagnostic performance as PET/CT. Nevertheless, further exploration of the potential added value of PET/MRI is necessary before clinical adoption of PET/MRI for epilepsy imaging.

MRI-identified abnormalities and wrist range of motion in asymptomatic versus symptomatic computer users.

BACKGROUND: Previous work has shown an association between restricted wrist range of motion (ROM) and upper extremity musculoskeletal disorders in computer users. We compared the prevalence of MRI-identified wrist abnormalities and wrist ROM between asymptomatic and symptomatic computer users. METHODS: MR images at 1.5 T of both wrists were obtained from 10 asymptomatic controls (8 F, 2 M) and 14 computer users (10 F, 4 M) with chronic wrist pain (10 bilateral; 4 right-side). Maximum wrist range of motion in flexion and radioulnar deviation was measured with an electrogoniometer. RESULTS: Extraosseous ganglia were identified in 66.6% of asymptomatic wrists and in 75% of symptomatic wrists. Intraosseous ganglia were identified in 45.8% of asymptomatic wrists and in 75% of symptomatic wrists, and were significantly (p < .05) larger in the symptomatic wrists. Distal ECU tendon instability was identified in 58.4% of both asymptomatic and symptomatic wrists. Dominant wrist flexion was significantly greater in the asymptomatic group (68.8 ± 6.7 deg.) compared to the symptomatic group (60.7 ± 7.3 deg.), p < .01. There was no significant correlation between wrist flexion and intraosseous ganglion burden (p = .09) CONCLUSIONS: This appears to be the first MRI study of wrist abnormalities in computer users.This study demonstrates that a variety of wrist abnormalities are common in computer users and that only intraosseous ganglia prevalence and size differed between asymptomatic and symptomatic wrists. Flexion was restricted in the dominant wrist of the symptomatic group, but the correlation between wrist flexion and intraosseous ganglion burden did not reach significance. Flexion restriction may be an indicator of increased joint loading, and identifying the cause may help to guide preventive and therapeutic interventions.

Evaluation of 511 keV photon attenuation by a novel 32-channel phased array prospectively designed for cardiovascular hybrid PET/MRI imaging.

BACKGROUND: Simultaneous cardiovascular imaging with positron emission tomography (PET) and magnetic resonance imaging (MRI) requires tools such as radio frequency (RF) phased arrays to achieve high temporal and spatial resolution in the MRI, as well as accurate quantification of PET. Today, high-density phased arrays (> 16 channels) used for cardiovascular PET/MRI are not designed to achieve low PET attenuation, and correcting the PET attenuation they cause requires off-line reconstruction, extra time and resources. PURPOSE: Motivated by previous work assessing the MRI performance of a novel prospectively designed 32-channel phased array, this study assessed the PET image quality with this array in place. Guided by NEMA standards, PET performance was measured using global PET counts, regional background variation (BV), contrast recovery (CR) and contrast-to-noise ratio (CNR) for both the novel array and standard arrays (mMR 12-channel and MRI 32-channel). Nonattenuation-corrected (NAC) data from all arrays (and each part of the array) were processed and compared to no-array, and relative percentage difference (RPD) of the global means was estimated and reported for each part of the arrays. Attenuation correction (AC) of PET images (water in the phantom) using two approaches, MR-based AC map (MRAC) and dual-energy CT-based map (DCTAC), was performed, and RPD compared for each part of the arrays. Percent mean attenuation within regions of interests of the phantom images from each array were compared using a two-way analysis of variance (ANOVA). RESULTS: The NAC data of the anterior part of the novel array recorded the least PET attenuation (≤ 2%); while the full novel array (anterior and posterior together) AC data, produced by MRAC and DCTAC approaches, recorded attenuation of 1.5 ± 2.9% and 0.0 ± 2.5%, respectively. The novel array PET count loss was significantly lower (p = 0.001) than those caused by the standard arrays. CONCLUSIONS: Results of this novel 32-channel cardiac array PET performance evaluation, together with its previously reported MRI performance assessment, suggest the novel array to be a strong alternative to the standard arrays currently used for cardiovascular hybrid PET/MRI imaging. It enables accurate PET quantification and high-temporal and spatial resolution for MR imaging.

DCE-MRI assessment of response to neoadjuvant SABR in early stage breast cancer: Comparisons of single versus three fraction schemes and two different imaging time delays post-SABR.

PURPOSE: To determine the effect of dose fractionation and time delay post-neoadjuvant stereotactic ablative radiotherapy (SABR) on dynamic contrast-enhanced (DCE)-MRI parameters in early stage breast cancer patients. MATERIALS AND METHODS: DCE-MRI was acquired in 17 patients pre- and post-SABR. Five patients were imaged 6-7 days post-21 Gy/1fraction (group 1), six 16-19 days post-21 Gy/1fraction (group 2), and six 16-18 days post-30 Gy/3 fractions every other day (group 3). DCE-MRI scans were performed using half the clinical dose of contrast agent. Changes in the surrounding tissue were quantified using a signal-enhancement threshold metric that characterizes changes in signal-enhancement volume (SEV). Tumour response was quantified using Ktrans and ve (Tofts model) pre- and post-SABR. Significance was assessed using a Wilcoxin signed-rank test. RESULTS: All group 1 and 4/6 group 2 patients' SEV increased post-SABR. All group 3 patients' SEV decreased. The mean Ktrans increased for group 1 by 76% (p = 0.043) while group 2 and 3 decreased 15% (p = 0.028) and 34% (p = 0.028), respectively. For ve, there was no significant change in Group 1 (p = 0.35). Groups 2 showed an increase of 24% (p = 0.043), and Group 3 trended toward an increase (23%, p = 0.08). CONCLUSION: Kinetic parameters measured 2.5 weeks post-SABR in both single fraction and three fraction groups were indicative of response but only the single fraction protocol led to enhancement in the surrounding tissue. Our results also suggest that DCE-MRI one-week post-SABR may be too early for response assessment, at least for single fraction SABR, whereas 2.5 weeks appears sufficiently long to minimize confounding acute effects.

Muscle metabolism and acid-base status during exercise in forearm work-related myalgia measured with 31P-MRS.

In this study, we examined muscle metabolic and acid-base status during incremental wrist extension exercise in the forearm of individuals with work-related myalgia (WRM). Eighteen women employed in full-time occupations involving repetitive forearm labor were recruited in this cross-sectional study. Nine of these women were diagnosed with WRM, while the other nine had no previous WRM history and were used as age-matched controls (Con). Phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) was used to noninvasively monitor the intracellular concentrations of phosphocreatine ([PCr]) and inorganic phosphate ([P(i)]) as well as intracellular pH (pH(i)) status during exercise in WRM and Con. We observed a 38% decreased work capacity in WRM compared with Con [0.18 W (SD 0.03) vs. 0.28 W (SD 0.10); P = 0.007]. Piecewise linear regression of the incremental exercise data revealed that the onset of a faster decrease in pH(i) (i.e., the pH threshold, pHT) and the onset of a faster increase in log([P(i)]/[PCr]) (i.e., the phosphorylation threshold, PT) occurred at a 14% relatively lower power output in WRM [pHT: 45.2% (SD 5.3) vs. 59.0% (SD 4.6), P < 0.001; PT: 44.8% (SD 4.3) vs. 57.8% (SD 3.1), P < 0.001; % of peak power output, Con vs. WRM, respectively]. Monoexponential modeling of the kinetics of [PCr] and pH(i) recovery following exercise demonstrated a slower (P = 0.005) time constant (tau) for [PCr] in WRM [113 s (SD 25)] vs. Con [77 s (SD 23)] and a slower (P = 0.007) tau for pH(i) in WRM [370 s (SD 178)] vs. Con [179 s (SD 52)]. In conclusion, our results suggest that WRM is associated with an increased reliance on nonoxidative metabolism. Possible mechanisms include a reduction in local muscle blood flow and perfusion, an increased ATP cost of force production, or both.

Females follow a more "compact" early human brain development model than males. A case-control study of preterm neonates.

The pattern of sexual differentiation of the human brain is not well understood, particularly at the early stages of development when intense growth and multiple maturational phenomena overlap and interrelate. A case-control study of 20 preterm males and females matched for age was conducted. Three-dimensional images were acquired with 3 T MRI. The cerebral volume and the cortical folding area (FA), defined as the surface area of the interface between cortical gray and white matter, were compared between males and females. Females had smaller cerebra than males even after removing the influence of overall size differences between the subjects. The cortical FA increased in relation to volume by a power of 4/3 in both groups. Females had larger cortical FA compared with males with similar cerebral volumes. The study provides in vivo evidence of sexually dimorphic early human brain development. The relatively more "compact" female model may well relate to sex differences in neural circuitry and cognitive domains.

Changes in cerebral oxygen consumption and high-energy phosphates during early recovery in hypoxic-ischemic piglets: a combined near-infrared and magnetic resonance spectroscopy study.

Near-infrared spectroscopy (NIRS) offers the ability to assess brain function at the bedside of critically ill neonates. Our group previously demonstrated a persistent reduction in the cerebral metabolic rate of oxygen (CMRO(2)) after hypoxia-ischemia (HI) in newborn piglets. The purpose of this current study was to determine the causes of this reduction by combining NIRS with magnetic resonance spectroscopy (MRS) to measure high-energy metabolites and diffusion-weighted imaging to measure cellular edema. Nine piglets were exposed to 30 min of HI and nine piglets served as controls. Proton and phosphorous MRS spectra, apparent diffusion coefficient (ADC) maps, and CMRO(2) measurements were collected periodically before and for 5.5 h after HI. A significant decrease in CMRO(2) (26 +/- 7%) was observed after HI. Incomplete recovery of nucleotide triphosphate concentration (8 +/- 3%

Assessment of a novel 32-channel phased array for cardiovascular hybrid PET/MRI imaging: MRI performance.

BACKGROUND: Cardiovascular imaging using hybrid positron emission tomography (PET) and magnetic resonance imaging (MRI) requires a radio frequency phased array resonator capable of high acceleration factors in order to achieve the shortest breath-holds while maintaining optimal MRI signal-to-noise ratio (SNR) and minimum PET photon attenuation. To our knowledge, the only two arrays used today for hybrid PET/MRI cardiovascular imaging are either incapable of achieving high acceleration or affect the PET photon count greatly. PURPOSE: This study is focused on the evaluation of the MRI performance of a novel third-party prototype 32-channel phased array designed for simultaneous PET/MRI cardiovascular imaging. The study compares the quality parameters of MRI parallel imaging, such as g-factor, noise correlation coefficients, and SNR, to the conventional arrays (mMR 12-channel and MRI-only 32-channel) currently used with hybrid PET/MRI systems. The quality parameters of parallel imaging were estimated for multiple acceleration factors on a phantom and three healthy volunteers. Using a Germanium-68 (Ge-68) phantom, preliminary measurements of PET photon attenuation caused by the novel array were briefly compared to the photon counts produced from no-array measurements. RESULTS: The global mean of the g-factor and SNRg produced by the novel 32-channel PET/MRI array were better than those produced by the MRI-only 32-channel array by 5% or more. The novel array has resulted in MRI SNR improvements of > 30% at all acceleration factors, in comparison to the mMR12-channel array. Preliminary evaluation of PET transparency showed less than 5% photon attenuation caused by both anterior and posterior parts of the novel array. CONCLUSIONS: The MRI performance of the novel PET/MRI 32-channel array qualifies it to be a viable alternative to the conventional arrays for cardiovascular hybrid PET/MRI. A detailed evaluation of the novel array's PET performance remains to be conducted, but cursory assessment promises significantly reduced attenuation.

MagA expression attenuates iron export activity in undifferentiated multipotent P19 cells.

Magnetic resonance imaging (MRI) is a non-invasive imaging modality used in longitudinal cell tracking. Previous studies suggest that MagA, a putative iron transport protein from magnetotactic bacteria, is a useful gene-based magnetic resonance contrast agent. Hemagglutinin-tagged MagA was stably expressed in undifferentiated embryonic mouse teratocarcinoma, multipotent P19 cells to provide a suitable model for tracking these cells during differentiation. Western blot and immunocytochemistry confirmed the expression and membrane localization of MagA in P19 cells. Surprisingly, elemental iron analysis using inductively-coupled plasma mass spectrometry revealed significant iron uptake in both parental and MagA-expressing P19 cells, cultured in the presence of iron-supplemented medium. Withdrawal of this extracellular iron supplement revealed unexpected iron export activity in P19 cells, which MagA expression attenuated. The influence of iron supplementation on parental and MagA-expressing cells was not reflected by longitudinal relaxation rates. Measurement of transverse relaxation rates (R2* and R2) reflected changes in total cellular iron content but did not clearly distinguish MagA-expressing cells from the parental cell type, despite significant differences in the uptake and retention of total cellular iron. Unlike other cell types, the reversible component R2' (R2* ‒ R2) provided only a moderately strong correlation to amount of cellular iron, normalized to amount of protein. This is the first report to characterize MagA expression in a previously unrecognized iron exporting cell type. The interplay between contrast gene expression and systemic iron metabolism substantiates the potential for diverting cellular iron toward the formation of a novel iron compartment, however rudimentary when using a single magnetotactic bacterial gene expression system like magA. Since relatively few mammalian cells export iron, the P19 cell line provides a tractable model of ferroportin activity, suitable for magnetic resonance analysis of key iron-handling activities and their influence on gene-based MRI contrast.

Validation study of a pulsed arterial spin labeling technique by comparison to perfusion computed tomography.

Abnormalities in cerebral blood flow (CBF) are believed to play a significant role in the development of major neonatal neuropathologies. One approach that would appear ideal for measuring CBF in this fragile age group is arterial spin labeling (ASL) since ASL techniques are noninvasive and quantitative. The purpose of this study was to assess the accuracy of a pulsed ASL method implemented on a 3-T scanner dedicated to neonatal imaging. Cerebral blood flow was measured in nine neonatal piglets, the ASL-CBF measurements were acquired at two inversion times (TI) (1,200 and 1,700 ms), and CBF was measured by perfusion computed tomography (pCT) for validation. Perfusion CT also provided images of cerebral blood volume, which were used to identify large blood vessels, and contrast arrival time, which were used to assess differences in arterial transit times between gray and white matter. Good agreement was found between gray matter CBF values from pCT (76+/-1 ml/min per 100 g) and ASL at TI=1,700 ms (73+/-1 ml/min per 100 g). At TI=1,200 ms, ASL overestimated CBF (91+/-2 ml/min per 100 g), which was attributed to substantial intravascular signal. No significant differences in white matter CBF from pCT and ASL were observed (average CBF=60+/-1 ml/min per 100 g), nor was there any difference in contrast arrival times for gray and white matter (0.95+/-0.04 and 0.99+/-0.03 s, respectively), which suggests that the arterial transit times for ASL were the same in this animal model. This study verified the accuracy of the implemented ASL technique and showed the value of using pCT to study other factors that can affect ASL-CBF measurements.

The effect of forearm posture on wrist flexion in computer workers with chronic upper extremity musculoskeletal disorders.

BACKGROUND: Occupational computer use has been associated with upper extremity musculoskeletal disorders (UEMSDs), but the etiology and pathophysiology of some of these disorders are poorly understood. Various theories attribute the symptoms to biomechanical and/or psychosocial stressors. The results of several clinical studies suggest that elevated antagonist muscle tension may be a biomechanical stress factor. Affected computer users often exhibit limited wrist range of motion, particularly wrist flexion, which has been attributed to increased extensor muscle tension, rather than to pain symptoms. Recreational or domestic activities requiring extremes of wrist flexion may produce injurious stress on the wrist joint and muscles, the symptoms of which are then exacerbated by computer use. As these activities may involve a variety of forearm postures, we examined whether changes in forearm posture have an effect on pain reports during wrist flexion, or whether pain would have a limiting effect on flexion angle. METHODS: We measured maximum active wrist flexion using a goniometer with the forearm supported in the prone, neutral, and supine postures. Data was obtained from 5 subjects with UEMSDs attributed to computer use and from 13 control subjects. RESULTS: The UEMSD group exhibited significantly restricted wrist flexion compared to the control group in both wrists at all forearm postures with the exception of the non-dominant wrist with the forearm prone. In both groups, maximum active wrist flexion decreased at the supine forearm posture compared to the prone posture. No UEMSD subjects reported an increase in pain symptoms during testing. CONCLUSION: The UEMSD group exhibited reduced wrist flexion compared to controls that did not appear to be pain related. A supine forearm posture reduced wrist flexion in both groups, but the reduction was approximately 100% greater in the UEMSD group. The effect of a supine forearm posture on wrist flexion is consistent with known biomechanical changes in the distal extensor carpi ulnaris tendon that occur with forearm supination. We infer from these results that wrist extensor muscle passive tension may be elevated in UEMSD subjects compared to controls, particularly in the extensor carpi ulnaris muscle. Measuring wrist flexion at the supine forearm posture may highlight flexion restrictions that are not otherwise apparent.