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Magnetic overlayers of Fe and Co have been investigated with x-ray magnetic circular dichroism in x-ray absorption spectroscopy and photoelectron spectroscopy, including spin-resolved photoelectron spectroscopy, at Beamline 4 at the Advanced Photon Source. Particular emphasis was placed upon the interrogation of the 2p levels of the Fe.
The scanning tunneling microscope (STM) has enabled manipulation and interrogation of surfaces with atomic-scale resolution. Electronic information about a surface is obtained by combining the imaging capability of the STM with scanning tunneling spectroscopy, i.e., measurement of current-voltage (I/V) characteristics of the surface. We propose a change in the STM feedback loop that enables capturing a higher quality dI/dV image. A high frequency dither voltage is added to the bias voltage of the sample, and the fundamental frequency component of the resulting current is demodulated. The in-phase component of this signal is then plotted along with the X and Y position data, constructing the dI/dV image. Here, we show that by incorporating notch filters in the STM feedback loop, we may utilize a high-amplitude dither voltage to significantly improve the quality of the obtained dI/dV image.
Sputter-deposited Pt-Au thin films have been reported to develop a hard, stable, nanocrystalline structure, yet little is known about how these characteristics vary with Pt x Au 1-x composition and process conditions. Toward this end, this document describes an extensive, combinatorial Pt-Au thin film library including characterized film compositions, structure, and properties. Complemented by kinematic Monte Carlo simulations of codeposition, a broad range of Pt x Au 1-x compositions (from x ~ 0.02 to 0.93) was first established by sputtering with varied magnetron powers and gun tilt angles. Further, the produced films were subsequently interrogated using automated nanoindentation, x-ray reflectivity, x-ray diffraction, atomic force microscopy, surface profilometry, four-point probe sheet resistance techniques, and wavelength dispersive spectroscopy in order to determine how hardness, modulus, density, surface roughness, structure, and resistivity vary with film stoichiometry and process parameters. Combinatorial films displayed an assortment of properties with the hardness of some films exceeding values reported previously for this material system. High hardness, high modulus, and low resistivity were generally attained when using increased deposition energy and reduced angle-of-incidence processes. Overall, the research identified promising, new Pt x Au 1-x compositions for future study and pinpointed strategies for improved deposition.
Nuclear materials often evolve into two-phase systems comprising a bulk matrix with dispersed inert-gas bubbles. The presence of these bubbles can have consequences to the thermomechanical response of materials and is a key life-limiting factor in some nuclear fuel forms. Understanding the behavior of these two-phase, bubble-matrix systems is, thus, important to improved predictive models and frameworks for many nuclear materials applications. While temperature excursions of these two-phase systems have been characterized, fewer studies have focused on the evolution of inert-gas bubbles under pressure. Here, in this paper, we use x-ray tools to interrogate a He-implanted gold foil to determine the pressure-dependent evolution of the individual components (Au matrix + bubbles), and we compare that total pressure dependence to theoretical equation-of-state descriptions based on mixing rules.
We report a fiber-optic sensor configuration with a cascaded fiber Bragg grating (FBG) and a silicon Fabry-Perot interferometer (FPI) for simultaneous measurement of temperature and strain. The sensor is composed of a 5 mm FBG on a single mode fiber and a 100μm thick silicon FPI attached to the tip of the optical fiber. The FBG is surface mounted on the host structure, and the FPI tip is suspended. Due to the stress-free, cantilever configuration, the silicon FPI is insensitive to strain, but sensitive to temperature with a sensitivity much higher than the FBG due to the large thermo-optic coefficient of silicon. The sensor is tested from room temperature to 100°C with varying strain up to ∼150με. The silicon FPI provides high temperature sensitivity of 89 pm/°C unaffected by strain. Since the FBG is attached to the host structure, it is affected by both thermal and mechanical strain; the sensitivity of these was experimentally obtained 32 pm/°C and 1.09 pm / με, respectively. Interrogated with a broadband light source and a high-speed spectrometer, the sensor shows temperature and strain resolutions of 1.9 × 10 −3 °C and 0.042 με, respectively. Here, due to the small size, enhanced sensitivity, and high resolution, this cascaded FBG-FPI sensor can be used in applications where accurate measurement of temperature and strain is required.
A novel fiber-optic probe measures the velocity distribution of an imploding surface along many lines of sight. Reflected light from each spot on the moving surface is Doppler shifted with a small portion of this light propagating backwards through the launching fiber. The reflected light is mixed with a reference laser in a technique called photon Doppler velocimetry, providing continuous time records. Within the probe, a matrix array of 56 single-mode fibers sends light through an optical relay consisting of three types of lenses. Seven sets of these relay lenses are grouped into a close-packed array allowing the interrogation of seven regions of interest. A six-faceted prism with a hole drilled into its center directs the light beams to the different regions. Several types of relay lens systems have been evaluated, including doublets and molded aspheric singlets. The optical design minimizes beam diameters and also provides excellent imaging capabilities. One of the fiber matrix arrays can be replaced by an imaging coherent bundle. This close-packed array of seven relay systems provides up to 476 beam trajectories. The pyramid prism has its six facets polished at two different angles that will vary the density of surface point coverage. Fibers in the matrix arrays are angle polished at 8{sup o} to minimize back reflections. This causes the minimum beam waist to vary along different trajectories. Precision metrology on the direction cosine trajectories is measured to satisfy environmental requirements for vibration and temperature.
Modern advanced energy systems such as coal-fired power plants, gasifiers, or similar infrastructure present some of the most challenging harsh environments for sensors. The power industry would benefit from new, ultra-high temperature devices capable of surviving in hot and corrosive environments for embedded sensing at the highest value locations. For these applications, we are currently exploring optical fiber evanescent wave absorption spectroscopy (EWAS) based sensors consisting of high temperature core materials integrated with novel high temperature gas sensitive cladding materials. Mathematical simulations can be used to assist in sensor development efforts, and we describe a simulation code that assumes a single thick cladding layer with gas sensitive optical constants. Recent work has demonstrated that Au nanoparticle-incorporated metal oxides show a potentially useful response for high temperature optical gas sensing applications through the sensitivity of the localized surface plasmon resonance absorption peak to ambient atmospheric conditions. Hence, the simulation code has been applied to understand how such a response can be exploited in an optical fiber based EWAS sensor configuration. We demonstrate that interrogation can be used to optimize the sensing response in such materials.
Purpose: Develop a method to subtract fat tissue contributions to wide-angle x-ray scatter (WAXS) signals of breast biopsies in order to estimate the differential linear scattering coefficients μ{sub s} of fatless tissue. Cancerous and fibroglandular tissue can then be compared independent of fat content. In this work phantom materials with known compositions were used to test the efficacy of the WAXS subtraction model. Methods: Each sample 5 mm in diameter and 5 mm thick was interrogated by a 50 kV 2.7 mm diameter beam for 3 min. A 25 mm{sup 2} by 1 mm thick CdTe detector allowed measurements of a portion of the θ = 6° scattered field. A scatter technique provided means to estimate the incident spectrum N{sub 0}(E) needed in the calculations of μ{sub s}[x(E, θ)] where x is the momentum transfer argument. Values of μ{sup ¯}{sub s} for composite phantoms consisting of three plastic layers were estimated and compared to the values obtained via the sum μ{sup ¯}{sub s}{sup ∑}(x)=ν{sub 1}μ{sub s1}(x)+ν{sub 2}μ{sub s2}(x)+ν{sub 3}μ{sub s3}(x), where ν{sub i} is the fractional volume of the ith plastic component. Water, polystyrene, and a volume mixture of 0.6 water + 0.4 polystyrene labelled as fibphan were chosen to mimic cancer, fat, and fibroglandular tissue, respectively. A WAXS subtraction model was used to remove the polystyrene signal from tissue composite phantoms so that the μ{sub s} of water and fibphan could be estimated. Although the composite samples were layered, simulations were performed to test the models under nonlayered conditions. Results: The well known μ{sub s} signal of water was reproduced effectively between 0.5 < x < 1.6 nm{sup −1}. The μ{sup ¯}{sub s} obtained for the heterogeneous samples agreed with μ{sup ¯}{sub s}{sup ∑}. Polystyrene signals were subtracted successfully from composite phantoms. The simulations validated the usefulness of the WAXS models for nonlayered biopsies. Conclusions: The methodology to measure μ{sub s} of homogeneous samples was quantitatively accurate. Simple WAXS models predicted the probabilities for specific x-ray scattering to occur from heterogeneous biopsies. The fat subtraction model can allow μ{sub s} signals of breast cancer and fibroglandular tissue to be compared without the effects of fat provided there is an independent measurement of the fat volume fraction ν{sub f}. Future work will consist of devising a quantitative x-ray digital imaging method to estimate ν{sub f} in ex vivo breast samples.
Purpose: The aims of this study are: (a) to investigate the capability of photoacoustic (PA) method in detecting high-intensity focused ultrasound (HIFU) treatments in muscle tissuesin vitro; and (b) to determine the optical properties of HIFU-treated and native tissues in order to assist in the interpretation of the observed contrast in PA detection of HIFU treatments. Methods: A single-element, spherically concaved HIFU transducer with a centre frequency of 1 MHz was utilized to create thermal lesions in chicken breast tissuesin vitro. To investigate the detectability of HIFU treatments photoacoustically, PA detection was performed at 720 and 845 nm on seven HIFU-treated tissue samples. Within each tissue sample, PA signals were acquired from 22 locations equally divided between two regions of interest within two volumes in tissue – a HIFU-treated volume and an untreated volume. Optical spectroscopy was then carried out on 10 HIFU-treated chicken breast specimens in the wavelength range of 500–900 nm, in 1-nm increments, using a spectrophotometer with an integrating sphere attachment. The authors’ optical spectroscopy raw data (total transmittance and diffuse reflectance) were used to obtain the optical absorption and reduced scattering coefficients of HIFU-induced thermal lesions and native tissues by employing the inverse adding-doubling method. The aforementioned interaction coefficients were subsequently used to calculate the effective attenuation coefficient and light penetration depth of HIFU-treated and native tissues in the wavelength range of 500–900 nm. Results: HIFU-treated tissues produced greater PA signals than native tissues at 720 and 845 nm. At 720 nm, the averaged ratio of the peak-to-peak PA signal amplitude of HIFU-treated tissue to that of native tissue was 3.68 ± 0.25 (mean ± standard error of the mean). At 845 nm, the averaged ratio of the peak-to-peak PA signal amplitude of HIFU-treated tissue to that of native tissue was 3.75 ± 0.26 (mean ± standard error of the mean). The authors’ spectroscopic investigation has shown that HIFU-treated tissues have a greater optical absorption and reduced scattering coefficients than native tissues in the wavelength range of 500–900 nm. In fact, at 720 and 845 nm, the ratio of the optical absorption coefficient of HIFU-treated tissues to that of native tissues was 1.13 and 1.17, respectively; on the other hand, the ratio of the reduced scattering coefficient of HIFU-treated tissues to that of native tissues was 13.22 and 14.67 at 720 and 845 nm, respectively. Consequently, HIFU-treated tissues have a higher effective attenuation coefficient and a lower light penetration depth than native tissues in the wavelength range 500–900 nm. Conclusions: Using a PA approach, HIFU-treated tissues interrogated at 720 and 845 nm optical wavelengths can be differentiated from untreated tissues. Based on the authors’ spectroscopic investigation, the authors conclude that the observed PA contrast between HIFU-induced thermal lesions and untreated tissue is due, in part, to the increase in the optical absorption coefficient, the reduced scattering coefficient and, therefore, the deposited laser energy fluence in HIFU-treated tissues.
Purpose: In many cancers, intratumoral heterogeneity exists in vascular and genetic structure. We developed an algorithm which uses clinical imaging to interrogate different scales of heterogeneity. We hypothesize that heterogeneity of perfusion at large distance scales may correlate with propensity for disease recurrence. We applied the algorithm to initial diagnosis MRI of rhabdomyosarcoma patients to predict recurrence. Methods: The Spatial Heterogeneity Analysis by Recursive Partitioning (SHARP) algorithm recursively segments the tumor image. The tumor is repeatedly subdivided, with each dividing line chosen to maximize signal intensity difference between the two subregions. This process continues to the voxel level, producing segments at multiple scales. Heterogeneity is measured by comparing signal intensity histograms between each segmented region and the adjacent region. We measured the scales of contrast enhancement heterogeneity of the primary tumor in 18 rhabdomyosarcoma patients. Using Cox proportional hazards regression, we explored the influence of heterogeneity parameters on relapse-free survival (RFS). To compare with existing methods, fractal and Haralick texture features were also calculated. Results: The complete segmentation produced by SHARP allows extraction of diverse features, including the amount of heterogeneity at various distance scales, the area of the tumor with the most heterogeneity at each scale, and for a given point in the tumor, the heterogeneity at different scales. 10/18 rhabdomyosarcoma patients suffered disease recurrence. On contrast-enhanced MRI, larger scale of maximum signal intensity heterogeneity, relative to tumor diameter, predicted for shorter RFS (p=0.05). Fractal dimension, fractal fit, and three Haralick features did not predict RFS (p=0.09-0.90). Conclusion: SHARP produces an automatic segmentation of tumor regions and reports the amount of heterogeneity at various distance scales. In rhabdomyosarcoma, RFS was shorter when the primary tumor exhibited larger scale of heterogeneity on contrast-enhanced MRI. If validated on a larger dataset, this imaging biomarker could be useful to help personalize treatment.
Purpose: To develop a method to estimate the mean fractional volume of fat (ν{sup ¯}{sub fat}) within a region of interest (ROI) of a tissue sample for wide-angle x-ray scatter (WAXS) applications. A scatter signal from the ROI was obtained and use of ν{sup ¯}{sub fat} in a WAXS fat subtraction model provided a way to estimate the differential linear scattering coefficient μ{sub s} of the remaining fatless tissue. Methods: The efficacy of the method was tested using animal tissue from a local butcher shop. Formalin fixed samples, 5 mm in diameter 4 mm thick, were prepared. The two main tissue types were fat and meat (fibrous). Pure as well as composite samples consisting of a mixture of the two tissue types were analyzed. For the latter samples, ν{sub fat} for the tissue columns of interest were extracted from corresponding pixels in CCD digital x-ray images using a calibration curve. The means ν{sup ¯}{sub fat} were then calculated for use in a WAXS fat subtraction model. For the WAXS measurements, the samples were interrogated with a 2.7 mm diameter 50 kV beam and the 6° scattered photons were detected with a CdTe detector subtending a solid angle of 7.75 × 10{sup −5} sr. Using the scatter spectrum, an estimate of the incident spectrum, and a scatter model, μ{sub s} was determined for the tissue in the ROI. For the composite samples, a WAXS fat subtraction model was used to estimate the μ{sub s} of the fibrous tissue in the ROI. This signal was compared to μ{sub s} of fibrous tissue obtained using a pure fibrous sample. Results: For chicken and beef composites, ν{sup ¯}{sub fat}=0.33±0.05 and 0.32 ± 0.05, respectively. The subtractions of these fat components from the WAXS composite signals provided estimates of μ{sub s} for chicken and beef fibrous tissue. The differences between the estimates and μ{sub s} of fibrous obtained with a pure sample were calculated as a function of the momentum transfer x. A t-test showed that the mean of the differences did not vary from zero in a statistically significant way thereby validating the methods. Conclusions: The methodology to estimate ν{sup ¯}{sub fat} in a ROI of a tissue sample via CCD x-ray imaging was quantitatively accurate. The WAXS fat subtraction model allowed μ{sub s} of fibrous tissue to be obtained from a ROI which had some fat. The fat estimation method coupled with the WAXS models can be used to compare μ{sub s} coefficients of fibroglandular and cancerous breast tissue.
Purpose: Pulmonary inflammation is associated with a variety of diseases. Assessing pulmonary inflammation on in vivo imaging may facilitate the early detection and treatment of lung diseases. Although routinely used in thoracic imaging, computed tomography has thus far not been compellingly shown to characterize inflammation in vivo. Alternatively, magnetic resonance imaging (MRI) is a nonionizing radiation technique to better visualize and characterize pulmonary tissue. Prior to routine adoption of MRI for early characterization of inflammation in humans, a rigorous and quantitative characterization of the utility of MRI to identify inflammation is required. Such characterization may be achieved by considering ex vivo histology as the ground truth, since it enables the definitive spatial assessment of inflammation. In this study, the authors introduce a novel framework to integrate 2D histology, ex vivo and in vivo imaging to enable the mapping of the extent of disease from ex vivo histology onto in vivo imaging, with the goal of facilitating computerized feature analysis and interrogation of disease appearance on in vivo imaging. The authors’ framework was evaluated in a preclinical preliminary study aimed to identify computer extracted features on in vivo MRI associated with chronic pulmonary inflammation. Methods: The authors’ image analytics framework first involves reconstructing the histologic volume in 3D from individual histology slices. Second, the authors map the disease ground truth onto in vivo MRI via coregistration with 3D histology using the ex vivo lung MRI as a conduit. Finally, computerized feature analysis of the disease extent is performed to identify candidate in vivo imaging signatures of disease presence and extent. Results: The authors evaluated the framework by assessing the quality of the 3D histology reconstruction and the histology—MRI fusion, in the context of an initial use case involving characterization of chronic inflammation in a mouse model. The authors’ evaluation considered three mice, two with an inflammation phenotype and one control. The authors’ iterative 3D histology reconstruction yielded a 70.1% ± 2.7% overlap with the ex vivo MRI volume. Across a total of 17 anatomic landmarks manually delineated at the division of airways, the target registration error between the ex vivo MRI and 3D histology reconstruction was 0.85 ± 0.44 mm, suggesting that a good alignment of the ex vivo 3D histology and ex vivo MRI had been achieved. The 3D histology-in vivo MRI coregistered volumes resulted in an overlap of 73.7% ± 0.9%. Preliminary computerized feature analysis was performed on an additional four control mice, for a total of seven mice considered in this study. Gabor texture filters appeared to best capture differences between the inflamed and noninflamed regions on MRI. Conclusions: The authors’ 3D histology reconstruction and multimodal registration framework were successfully employed to reconstruct the histology volume of the lung and fuse it with in vivo MRI to create a ground truth map for inflammation on in vivo MRI. The analytic platform presented here lays the framework for a rigorous validation of the identified imaging features for chronic lung inflammation on MRI in a large prospective cohort.
Purpose: Different approaches have been used in dynamic elastography to assess mechanical properties of biological tissues. Most techniques are based on a simple inversion based on the measurement of the shear wave speed to assess elasticity, whereas some recent strategies use more elaborated analytical or finite element method (FEM) models. In this study, a new method is proposed for the quantification of both shear storage and loss moduli of confined lesions, in the context of breast imaging, using adaptive torsional shear waves (ATSWs) generated remotely with radiation pressure. Methods: A FEM model was developed to solve the inverse wave propagation problem and obtain viscoelastic properties of interrogated media. The inverse problem was formulated and solved in the frequency domain and its robustness to noise and geometric constraints was evaluated. The proposed model was validated in vitro with two independent rheology methods on several homogeneous and heterogeneous breast tissue-mimicking phantoms over a broad range of frequencies (up to 400 Hz). Results: Viscoelastic properties matched benchmark rheology methods with discrepancies of 8%–38% for the shear modulus G′ and 9%–67% for the loss modulus G″. The robustness study indicated good estimations of storage and loss moduli (maximum mean errors of 19% on G′ and 32% on G″) for signal-to-noise ratios between 19.5 and 8.5 dB. Larger errors were noticed in the case of biases in lesion dimension and position. Conclusions: The ATSW method revealed that it is possible to estimate the viscoelasticity of biological tissues with torsional shear waves when small biases in lesion geometry exist.
Purpose: The GE SIGNA PET/MR is a new whole body integrated time-of-flight (ToF)-PET/MR scanner from GE Healthcare. The system is capable of simultaneous PET and MR image acquisition with sub-400 ps coincidence time resolution. Simultaneous PET/MR holds great potential as a method of interrogating molecular, functional, and anatomical parameters in clinical disease in one study. Despite the complementary imaging capabilities of PET and MRI, their respective hardware tends to be incompatible due to mutual interference. In this work, the GE SIGNA PET/MR is evaluated in terms of PET performance and the potential effects of interference from MRI operation. Methods: The NEMA NU 2-2012 protocol was followed to measure PET performance parameters including spatial resolution, noise equivalent count rate, sensitivity, accuracy, and image quality. Each of these tests was performed both with the MR subsystem idle and with continuous MR pulsing for the duration of the PET data acquisition. Most measurements were repeated at three separate test sites where the system is installed. Results: The scanner has achieved an average of 4.4, 4.1, and 5.3 mm full width at half maximum radial, tangential, and axial spatial resolutions, respectively, at 1 cm from the transaxial FOV center. The peak noise equivalent count rate (NECR) of 218 kcps and a scatter fraction of 43.6% are reached at an activity concentration of 17.8 kBq/ml. Sensitivity at the center position is 23.3 cps/kBq. The maximum relative slice count rate error below peak NECR was 3.3%, and the residual error from attenuation and scatter corrections was 3.6%. Continuous MR pulsing had either no effect or a minor effect on each measurement. Conclusions: Performance measurements of the ToF-PET whole body GE SIGNA PET/MR system indicate that it is a promising new simultaneous imaging platform.
Purpose: Recent legislative and accreditation requirements have driven rapid development and implementation of CT radiation dose monitoring solutions. Institutions must determine how to improve quality, safety, and consistency of their clinical performance. The purpose of this work was to design a strategy and meaningful characterization of results from an in-house, clinically-deployed dose monitoring solution. Methods: A dose monitoring platform was designed by our imaging physics group that focused on extracting protocol parameters, dose metrics, and patient demographics and size. Compared to most commercial solutions, which focus on individual exam alerts and global thresholds, the program sought to characterize overall consistency and targeted thresholds based on eight analytic interrogations. Those were based on explicit questions related to protocol application, national benchmarks, protocol and size-specific dose targets, operational consistency, outliers, temporal trends, intra-system variability, and consistent use of electronic protocols. Using historical data since the start of 2013, 95% and 99% intervals were used to establish yellow and amber parameterized dose alert thresholds, respectively, as a function of protocol, scanner, and size. Results: Quarterly reports have been generated for three hospitals for 3 quarters of 2015 totaling 27880, 28502, 30631 exams, respectively. Four adult and two pediatric protocols were higher than external institutional benchmarks. Four protocol dose levels were being inconsistently applied as a function of patient size. For the three hospitals, the minimum and maximum amber outlier percentages were [1.53%,2.28%], [0.76%,1.8%], [0.94%,1.17%], respectively. Compared with the electronic protocols, 10 protocols were found to be used with some inconsistency. Conclusion: Dose monitoring can satisfy requirements with global alert thresholds and patient dose records, but the real value is in optimizing patient-specific protocols, balancing image quality trade-offs that dose-reduction strategies promise, and improving the performance and consistency of a clinical operation. Data plots that capture patient demographics and scanner performance demonstrate that value.
Purpose: Cerenkov emission (CE) is a promising tool for online tumor microenvironment interrogation and targeting during radiotherapy. In this work, we utilize CE generated during radiotherapy as a broadband excitation source for real-time absorption spectroscopy. We demonstrate the feasibility of CE spectroscopy using a controlled experiment of materials with known emission/absorption properties. Methods: A water tank is irradiated with 20 MeV electron beam to induce Cerenkov emission. Food coloring dyes (Yellow #5, Red #40, and Blue #1), which have known emission/absorption properties were added to the water tank with increasing concentration (1 drop (0.05 mL), 2 drops, and 4 drops from a dispenser bottle). The signal is collected using a condensing lens which is coupled into a 20m optical fiber that is fed into a spectrometer that measures the emitted spectra. The resulting spectra from water/food coloring dye solutions were normalized by the reference spectrum, which is the Cerenkov spectrum of pure water, correcting for both the nonlinearity of the broadband Cerenkov emission spectrum as well as the non-uniform spectral response of the spectrometer. The emitted spectra were then converted into absorbance and their characteristics were analyzed. Results: The food coloring dye had a drastic change on the Cerenkov emission, shifting its wavelength according to its visible color. The collected spectra showed various absorbance peaks which agrees with tabulated peak positions of the dyes added within 0.3% for yellow, 1.7% for red, and 0.16% for blue. The CE peak heights proportionally increased as the dye concentration is increased. Conclusion: This work shows the potential for real-time functional spectroscopy using Cerenkov emission during radiotherapy. It was demonstrated that molecule identification as well as relative concentration can be extracted from the Cerenkov emission color shift.
This letter reports on the integration of eight ultrasonic transducers into a build substrate for individual in-process monitoring of eight parts fabricated using powder bed fusion additive manufacturing. Ultrasound is shown to be able to sense poor fusion of parts to the substrate and also sensitivity to porosity. This technique demonstrates the utility of ultrasound as one of a few techniques able to interrogate the volume of additively manufactured parts during the process. Additionally, the ability to measure several parts during a single build can be used for efficient process parameter development studies, as the ultrasonic measurements can offer rapid information about part quality and integrity.
Peroxisome proliferator-activated gamma coactivator 1-α (PGC1α) regulates energy metabolism by directly interacting with transcription factors to modulate gene expression. Among the PGC1α binding partners is liver receptor homolog 1 (LRH-1; NR5A2), an orphan nuclear hormone receptor that controls lipid and glucose homeostasis. Although PGC1α is known to bind and activate LRH-1, mechanisms through which PGC1α changes LRH-1 conformation to drive transcription are unknown. Here, we used biochemical and structural methods to interrogate the LRH-1–PGC1α complex. Purified, full-length LRH-1, as well as isolated ligand binding domain, bound to PGC1α with higher affinity than to the coactivator, nuclear receptor coactivator-2 (Tif2), in coregulator peptide recruitment assays. We present the first crystal structure of the LRH-1–PGC1α complex, which depicts several hydrophobic contacts and a strong charge clamp at the interface between these partners. In molecular dynamics simulations, PGC1α induced correlated atomic motion throughout the entire LRH-1 activation function surface, which was dependent on charge-clamp formation. In contrast, Tif2 induced weaker signaling at the activation function surface than PGC1α but promoted allosteric signaling from the helix 6/β-sheet region of LRH-1 to the activation function surface. These studies are the first to probe mechanisms underlying the LRH-1–PGC1α interaction and may illuminate strategies for selective therapeutic targeting of PGC1α-dependent LRH-1 signaling pathways.